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Asian women with PCOS have enhanced ovarian reserve and ART outcomes, even at an advanced maternal age: a model for reproductive longevity? 亚洲多囊卵巢综合征妇女卵巢储备能力和抗逆转录病毒治疗效果增强,即使在高龄产妇:生殖寿命的模型?
IF 11.1 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-10-14 eCollection Date: 2025-01-01 DOI: 10.1093/hropen/hoaf062
Qian Yang, Paula Benny, Jovin Jie Ning Lee, Devi Natalie Nadjaja, Shaili P Sashidharan, Eu-Leong Yong, Mahesh Choolani, Stephen Chew, Ling-Jun Li, Peng Cheang Wong, Zhongwei Huang
<p><strong>Study question: </strong>Does polycystic ovary syndrome (PCOS) represent a human model for reproductive longevity?</p><p><strong>Summary answer: </strong>Asian women with PCOS have enhanced ovarian reserve and ART outcomes, even at an advanced maternal age.</p><p><strong>What is known already: </strong>PCOS afflicts 4-20% of women at reproductive age and is associated with anovulation, hyperandrogenism, and polycystic ovarian morphology. However, there remains a paucity in research into the PCOS-related reproductive outcomes in Asian women following ART. This study addresses a critical gap in elucidating the Asian PCOS phenotype and reproductive longevity associated with PCOS, within the context of a multi-ethnic Asian population.</p><p><strong>Study design size duration: </strong>A retrospective observational cohort with a total of 3092 women from a tertiary-care centre in Singapore was analysed in this study.</p><p><strong>Participants/materials setting methods: </strong>PCOS was diagnosed according to the 2003 Rotterdam Criteria. After exclusions, 1249 women were grouped into the PCOS (n = 212) or normo-ovulatory (n = 1037) groups. Clinical demographics, ART protocols, reproductive outcomes, and hormone levels were evaluated in the study. Modified Poisson Regression analyses were used to compare the ART outcomes between PCOS and normo-ovulatory groups.</p><p><strong>Main results and the role of chance: </strong>Women with PCOS exhibit elevated levels of anti-Müllerian hormone (AMH) in comparison to normo-ovulatory women. While AMH levels typically decreased with age, the decline was observed to be significantly slower in women with PCOS when compared to their normo-ovulatory counterparts. Even after the age of 36 years, women with PCOS maintained relatively higher AMH levels (PCOS vs normo-ovulatory: 44.4 vs 19.3 pmol/l). The cumulative pregnancy rate following one ovarian stimulation cycle of ART decreased with age in normo-ovulatory women after 30 years old: 46.0% for ages 31-35 and 28.6% for ages 36 and older (<i>P</i> < 0.001). Conversely, for women with PCOS following ART, cumulative pregnancy rates remained stable in advanced maternal age, namely 56.7% for ages 31-35 and 55.9% for ages 36 and older. Compared with the normo-ovulatory group, the adjusted relative risk (aRR) of cumulative pregnancy rates in the PCOS group was significantly higher for women aged 36 years and older undergoing ART (aRR: 1.78; 95% CI: 1.24-2.54), especially for those undergoing IVF (2.01; 1.40-3.14).</p><p><strong>Limitations reasons for caution: </strong>This retrospective study included only Asian women, and hence this may not be applicable to other non-Asian populations.</p><p><strong>Wider implications of the findings: </strong>Our findings provide strong support for our hypothesis that women with PCOS may exhibit an extended reproductive life span and could attain successful pregnancy outcomes through ART, even at advanced maternal ages. These r
研究问题:多囊卵巢综合征(PCOS)是否代表了人类的生殖寿命模式?摘要回答:亚洲的多囊卵巢综合征患者卵巢储备能力和ART治疗效果都有所提高,即使是高龄产妇。已知情况:4-20%的育龄妇女患有多囊卵巢综合征,与无排卵、雄激素过多和多囊卵巢形态有关。然而,对亚洲妇女接受抗逆转录病毒治疗后与pcos相关的生殖结果的研究仍然缺乏。本研究解决了在多种族亚洲人群中阐明亚洲多囊卵巢综合征表型和与多囊卵巢综合征相关的生殖寿命的关键空白。研究设计规模持续时间:本研究分析了来自新加坡一家三级护理中心的3092名女性的回顾性观察队列。受试者/材料设置方法:根据2003年鹿特丹标准诊断多囊卵巢综合征。排除后,1249名妇女被分为多囊卵巢综合征组(n = 212)和排卵正常组(n = 1037)。在研究中评估了临床人口统计学、抗逆转录病毒治疗方案、生殖结果和激素水平。采用修正泊松回归分析比较PCOS组和正常排卵组的ART结果。主要结果和机会的作用:与排卵正常的妇女相比,PCOS妇女表现出抗勒氏激素(AMH)水平升高。虽然AMH水平通常会随着年龄的增长而下降,但与排卵正常的女性相比,PCOS女性的下降速度要慢得多。即使在36岁之后,多囊卵巢综合征(PCOS)女性的AMH水平仍然相对较高(PCOS vs正常排卵:44.4 vs 19.3 pmol/l)。30岁以后排卵正常的女性在接受一个卵巢刺激周期ART治疗后的累计妊娠率随着年龄的增长而下降:31-35岁为46.0%,36岁及以上为28.6% (P)。注意的局限性:本回顾性研究仅包括亚洲女性,因此可能不适用于其他非亚洲人群。研究结果的更广泛意义:我们的研究结果为我们的假设提供了强有力的支持,即PCOS女性可能表现出更长的生殖寿命,即使在高龄产妇中,也可以通过ART获得成功的妊娠结局。这些结果表明,多囊卵巢综合征(PCOS)女性的生殖寿命可能会延长,需要进一步的前瞻性纵向研究来揭示多囊卵巢综合征(PCOS)女性生殖寿命延长的机制。研究经费/竞争利益:本研究部分由新加坡国立大学bias - echo亚洲生殖寿命和平等中心资助。所有作者声明不存在利益竞争。试验注册号:NA。
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引用次数: 0
Microbiome dysbiosis and endometriosis: a systematic scoping review of current literature and knowledge gaps. 微生物群失调和子宫内膜异位症:当前文献和知识差距的系统范围审查。
IF 11.1 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-10-01 eCollection Date: 2025-01-01 DOI: 10.1093/hropen/hoaf061
Federica Facciotti, Giorgia Di Stefano, Paola Maragno, Claudia Ferraro, Dhouha Dridi, Edgardo Somigliana, Paola Viganò, Paolo Vercellini, Maíra Casalechi

Study question: What is the evidence available concerning gut and reproductive tract microbiomes in patients with endometriosis and what are the methodological approaches employed in microbiome studies on endometriosis?

Summary answer: The taxonomic profiles exhibited pronounced heterogeneity within women with and also within women without endometriosis across reviewed studies for all the anatomical districts evaluated.

What is known already: Both human and animal studies support differences in the microbiome composition of individuals with and without endometriosis. Endometriosis onset occurs with variable symptoms and manifestations. The microbiome composition at different sites may contribute to this variability.

Study design size duration: We used the scoping review methodology. Systematic searches of studies from the PubMed, EMBASE, and Web of Science databases published between 1 January 2016 and 1 November 2024 addressing endometriosis microbiome characterization in: (i) gut, (ii) vaginal fluid, (iii) cervical fluid, (iv) peritoneal fluid, (v) uterine fluid, (vi) ovarian cyst fluid, (vii) oropharyngeal fluid, and (viii) eutopic and (ix) ectopic tissues were performed using a combination of MeSH terms. References from relevant publications were systematically screened.

Participants/materials setting methods: Results were reported in accordance with the PRISMA-ScR guidelines. Studies that did not report original data, not written in English or providing a review of the field were excluded. From the 2182 publications retrieved, 36 papers were selected and analyzed, focusing on sample characterization (patients, controls, tissues, and fluids) and methodologies used.

Main results and the role of chance: Sound evidence is lacking to support a specific gut dysbiosis profile in women with endometriosis. The largest metagenome study performed using shotgun sequencing and controlling for multiple hypotheses testing did not detect significant differences between women with and without the disease. For eutopic and ectopic tissue microbiomes, the literature is too scant to draw any conclusion. Some data suggest a possible enrichment of Streptococcus sp. in cervical fluid and of Pseudomonas sp. in peritoneal fluid and a depletion of Lachnospira sp. in stool/anal fluid of endometriosis patients. However, these findings may be explained by confounders or by intrinsic patient or population characteristics. We appraised the limitations of the studies and proposed suggestions for optimizing sequencing techniques and experimental designs.

Limitations reasons for caution: The number of participants per study greatly varied and, with few exceptions, was typically low. Incomplete information on methodological approaches was broadly observed. The impact of participants' menstrual cycle p

研究问题:关于子宫内膜异位症患者肠道和生殖道微生物组的现有证据是什么?子宫内膜异位症微生物组研究采用的方法学方法是什么?总结性回答:在所有解剖区评估的回顾性研究中,有子宫内膜异位症的女性和没有子宫内膜异位症的女性的分类学特征表现出明显的异质性。已知情况:人类和动物研究都支持患有和未患有子宫内膜异位症的个体在微生物组组成上的差异。子宫内膜异位症发病时有不同的症状和表现。不同位置的微生物组组成可能导致这种差异。研究设计规模和持续时间:我们采用范围评估方法。系统检索了2016年1月1日至2024年11月1日期间发表的PubMed、EMBASE和Web of Science数据库中关于子宫内膜异位症微生物组特征的研究:(i)肠道,(ii)阴道液,(iii)宫颈液,(iv)腹膜液,(v)子宫液,(vi)卵巢囊肿液,(vii)口咽液,以及(viii)异位和(ix)异位组织。系统地筛选了有关出版物的参考文献。受试者/材料设置方法:按照PRISMA-ScR指南报告结果。未报告原始数据、未以英文撰写或未提供该领域综述的研究被排除。从检索到的2182份出版物中,选择并分析了36篇论文,重点关注样品表征(患者、对照、组织和液体)和使用的方法。主要结果和偶然性的作用:缺乏可靠的证据来支持子宫内膜异位症女性特定的肠道生态失调。使用霰弹枪测序和控制多重假设检验进行的最大的宏基因组研究没有发现患有和没有疾病的妇女之间的显着差异。对于异位和异位组织微生物组,文献太少,无法得出任何结论。一些资料提示子宫内膜异位症患者宫颈液中链球菌和腹膜液中假单胞菌可能丰富,粪便/肛门液中鞭毛螺旋体可能缺失。然而,这些发现可能由混杂因素或患者或人群的内在特征来解释。我们评估了研究的局限性,并提出了优化测序技术和实验设计的建议。注意的局限性:每项研究的参与者数量差异很大,除了少数例外,通常都很低。普遍观察到关于方法学方法的资料不完整。参与者的月经周期阶段、饮食和药物假设的影响通常没有被考虑。研究结果的更广泛影响:需要对研究方案进行标准化,以允许可重复性,并需要开展合作,以协调数据分析、解释,更重要的是,协调健康结果的预测或改善。研究资助/竞争利益:该审查由意大利卫生部资助:RF-2019-12369460和当前研究IRCCS。P.Vi。担任《子宫内膜异位症和子宫疾病杂志》主编。E.S.担任Human Reproduction Open的主编,并公开Ferring, Ibsa, Gedeon Richter和Theramex的研究资助,以及Ibsa和Gedeon Richter的酬金。P.Ve。担任Human Reproduction Open的副主编;是《加拿大妇产科杂志》、《意大利妇产科杂志》和《斯堪的纳维亚妇产科学报》国际编辑委员会的成员;在临床决策支持资源UpToDate中获得威科集团关于子宫内膜异位症管理章节的版税;同时拥有一家公立和私立妇科诊所。所有其他作者声明他们没有利益冲突。注册号:10.17605/OSF。IO/X6HBT在https://osf.io/registries。
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引用次数: 0
The functional ovarian anatomy of 492 women aged 18-22 years: a population-based study in Norway. 492名18-22岁女性卵巢功能解剖:挪威一项基于人群的研究。
IF 11.1 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-09-24 eCollection Date: 2025-01-01 DOI: 10.1093/hropen/hoaf057
Mari Landås Warp, Karoline Hansen Skåra, Thea Karoline Grindstad, Kirstine Kirkegaard, Nils-Halvdan Morken, Cecilia Høst Ramlau-Hansen, Liv Bente Romundstad, Siri Eldevik Håberg, Hans Ivar Hanevik
<p><strong>Study question: </strong>How do measures of functional ovarian anatomy (ovarian volume, antral follicle count, endocrinological profile) vary among women between 18 and 22 years?</p><p><strong>Summary answer: </strong>We found considerable inter-individual variability in functional ovarian anatomy in young adult females examined after puberty but before the age-related decline in ovarian function sets in.</p><p><strong>What is known already: </strong>Functional ovarian anatomy varies with age and disease. Fecundability in healthy females peaks in early adulthood when puberty is completed and the age-related decline in ovarian function is insignificant.</p><p><strong>Study design size duration: </strong>Daughters born into a population-based pregnancy study, The Norwegian Mother, Father and Child Cohort Study (MoBa) were examined on menstrual cycle days 2-5. Recruitment to this cross-sectional study started in August 2021 and is ongoing.</p><p><strong>Participants/materials setting methods: </strong>The 492 participants were aged 18-22 years and were not using hormonal contraceptives when they underwent a clinical examination during the early follicular phase of their menstrual cycle. Another group of 8146 MoBa daughters who were of similar age and who answered a questionnaire were studied to assess representativeness. Participants contributed with fasting blood samples, anthropometric measurements, and a questionnaire. Trained clinicians performed a transvaginal ultrasound to assess ovarian anatomy.</p><p><strong>Main results and the role of chance: </strong>The interquartile range was 9.3-17.2 cm<sup>3</sup> for total ovarian volume, 21-37 for total antral follicle count (AFC), and 16.0-35.4 pmol/l for serum anti-Müllerian hormone (AMH). We found positive correlations between ovarian volume and AFC (r = 0.52, <i>P</i> < 0.01), between ovarian volume and AMH (r = 0.53, <i>P</i> < 0.01), and between AFC and AMH (r = 0.71, <i>P</i> < 0.01). Participants' mean left ovarian volume (6.5 cm³, 95% CI: 6.1-6.8) and mean right ovarian volume (7.4 cm³, 95% CI: 7.1-7.8) differed (t(446) = 4.8, <i>P</i> < 0.001). The examined population was representative of the broader MoBa daughters population.</p><p><strong>Limitations reasons for caution: </strong>The study is ongoing and has a low participation rate possibly due to the intimate nature of the clinical examinations.</p><p><strong>Wider implications of the findings: </strong>There are large differences between young women in terms of functional ovarian anatomy. Follow-up of reproductive outcomes for these women, with linkage to the medical birth registry of Norway, could detect early signs of reduced fertility already in young adulthood.</p><p><strong>Study funding/competing interests: </strong>This study was funded by the Norwegian Institute of Public Health, Oslo, Norway, and by Telemark Hospital Trust, Porsgrunn, Norway, and was partly supported by the Research Council of Norway through its c
研究问题:18 - 22岁女性的功能性卵巢解剖(卵巢体积、卵泡计数、内分泌特征)有何差异?摘要回答:我们发现,在青春期后但在卵巢功能年龄相关衰退开始之前检查的年轻成年女性的卵巢功能解剖中,存在相当大的个体间差异。已知情况:卵巢功能解剖随年龄和疾病而变化。健康女性的生育能力在青春期结束后的成年早期达到顶峰,与年龄相关的卵巢功能下降不明显。研究设计规模持续时间:在基于人群的妊娠研究中出生的女儿,挪威母亲,父亲和儿童队列研究(MoBa)在月经周期第2-5天进行检查。这项横断面研究的招募于2021年8月开始,目前正在进行中。参与者/材料设置方法:492名参与者年龄在18-22岁之间,在月经周期的早期卵泡期接受临床检查时未使用激素避孕药。另一组8146名年龄相近的MoBa女儿回答了一份调查问卷,以评估代表性。参与者提供空腹血液样本、人体测量和问卷调查。训练有素的临床医生进行经阴道超声评估卵巢解剖。主要结果及影响因素:卵巢总体积9.3 ~ 17.2 cm3,卵泡总计数(AFC) 21 ~ 37,血清抗勒氏激素(AMH) 16.0 ~ 35.4 pmol/l。我们发现卵巢体积与AFC呈正相关(r = 0.52, P P P P P P)。注意的局限性:该研究仍在进行中,由于临床检查的密切性,参与率较低。研究结果的更广泛含义:在卵巢功能解剖方面,年轻女性之间存在很大差异。对这些妇女的生殖结果进行跟踪调查,并与挪威的医疗出生登记处联系起来,可以发现在成年早期就已经出现生育能力下降的早期迹象。研究经费/竞争利益:本研究由挪威奥斯陆的挪威公共卫生研究所和挪威Porsgrunn的Telemark医院信托基金资助,并由挪威研究理事会通过其卓越资助计划中心(项目号262700和项目号262700)提供部分支持。320656. 该项目由欧盟(EU)(欧洲研究理事会(ERC), BIOSFER, 101071773)共同资助。然而,所表达的观点和意见仅代表作者的观点和意见,并不一定反映欧盟或ERC的观点和意见。欧盟和授权机构都不能对此负责。作者报告没有利益冲突。试验注册号:无。
{"title":"The functional ovarian anatomy of 492 women aged 18-22 years: a population-based study in Norway.","authors":"Mari Landås Warp, Karoline Hansen Skåra, Thea Karoline Grindstad, Kirstine Kirkegaard, Nils-Halvdan Morken, Cecilia Høst Ramlau-Hansen, Liv Bente Romundstad, Siri Eldevik Håberg, Hans Ivar Hanevik","doi":"10.1093/hropen/hoaf057","DOIUrl":"10.1093/hropen/hoaf057","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;How do measures of functional ovarian anatomy (ovarian volume, antral follicle count, endocrinological profile) vary among women between 18 and 22 years?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;We found considerable inter-individual variability in functional ovarian anatomy in young adult females examined after puberty but before the age-related decline in ovarian function sets in.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Functional ovarian anatomy varies with age and disease. Fecundability in healthy females peaks in early adulthood when puberty is completed and the age-related decline in ovarian function is insignificant.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;Daughters born into a population-based pregnancy study, The Norwegian Mother, Father and Child Cohort Study (MoBa) were examined on menstrual cycle days 2-5. Recruitment to this cross-sectional study started in August 2021 and is ongoing.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;The 492 participants were aged 18-22 years and were not using hormonal contraceptives when they underwent a clinical examination during the early follicular phase of their menstrual cycle. Another group of 8146 MoBa daughters who were of similar age and who answered a questionnaire were studied to assess representativeness. Participants contributed with fasting blood samples, anthropometric measurements, and a questionnaire. Trained clinicians performed a transvaginal ultrasound to assess ovarian anatomy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;The interquartile range was 9.3-17.2 cm&lt;sup&gt;3&lt;/sup&gt; for total ovarian volume, 21-37 for total antral follicle count (AFC), and 16.0-35.4 pmol/l for serum anti-Müllerian hormone (AMH). We found positive correlations between ovarian volume and AFC (r = 0.52, &lt;i&gt;P&lt;/i&gt; &lt; 0.01), between ovarian volume and AMH (r = 0.53, &lt;i&gt;P&lt;/i&gt; &lt; 0.01), and between AFC and AMH (r = 0.71, &lt;i&gt;P&lt;/i&gt; &lt; 0.01). Participants' mean left ovarian volume (6.5 cm³, 95% CI: 6.1-6.8) and mean right ovarian volume (7.4 cm³, 95% CI: 7.1-7.8) differed (t(446) = 4.8, &lt;i&gt;P&lt;/i&gt; &lt; 0.001). The examined population was representative of the broader MoBa daughters population.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations reasons for caution: &lt;/strong&gt;The study is ongoing and has a low participation rate possibly due to the intimate nature of the clinical examinations.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Wider implications of the findings: &lt;/strong&gt;There are large differences between young women in terms of functional ovarian anatomy. Follow-up of reproductive outcomes for these women, with linkage to the medical birth registry of Norway, could detect early signs of reduced fertility already in young adulthood.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study funding/competing interests: &lt;/strong&gt;This study was funded by the Norwegian Institute of Public Health, Oslo, Norway, and by Telemark Hospital Trust, Porsgrunn, Norway, and was partly supported by the Research Council of Norway through its c","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 4","pages":"hoaf057"},"PeriodicalIF":11.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12478698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202248","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
Decoding uterine (dys)function in fibroids through multimodal assessment of functional determinants: a systematic review and meta-analysis. 通过功能决定因素的多模态评估来解码子宫肌瘤的功能:一项系统回顾和荟萃分析。
IF 11.1 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-09-18 eCollection Date: 2025-01-01 DOI: 10.1093/hropen/hoaf060
Noemi Salmeri, Edgardo Somigliana, Alexander Fiore, Davide Marinello, Benedetta Maizza, Francesca Filippi, Paola Viganò, Fabio Parazzini
<p><strong>Study question: </strong>Is there a difference in uterine functional determinants between women with fibroids and women without myometrial pathology?</p><p><strong>Summary answer: </strong>Women with uterine fibroids consistently exhibit altered uterine functional determinants compared to controls, characterized by increased perfusion, elevated stiffness, and impaired contractility.</p><p><strong>What is known already: </strong>The functional determinants of the non-pregnant uterus remain largely unexplored and underreported. Uterine fibroids, as a well-defined morphological myometrial pathology, offer a unique model for understanding uterine functionality.</p><p><strong>Study design size duration: </strong>This systematic review and meta-analysis included original articles published in English and indexed in PubMed, Embase, and Scopus databases up to 20 December 2024. The search strategy combined terms related to uterine fibroids with those describing uterine functional parameters (e.g. uterine vascularity, stiffness, and contractility), together with diagnostic methods (including Doppler ultrasound, elastography, and magnetic resonance imaging).</p><p><strong>Participants/materials setting methods: </strong>Observational studies evaluating quantitative uterine functional determinants in non-pregnant women with fibroids and controls without myometrial pathology were selected using predefined Population, Intervention (Investigated measure), Comparator, Outcome(s), Study type (PICOS) criteria. Outcomes included quantitative measures of uterine functionality such as vascularization (uterine artery Doppler indices), stiffness (elastography parameters), and contractility (peristalsis parameters). Study quality was evaluated using the Newcastle-Ottawa Scale. Pooled estimates for continuous outcomes were calculated using random-effects models, expressed as mean difference (MD) with 95% CIs. Subgroup analyses addressed potential confounders, including menopausal status, hormonal therapy use, and symptom severity.</p><p><strong>Main results and the role of chance: </strong>Fourteen studies met the inclusion criteria: seven on vascularization (n = 961), five on stiffness (n = 342), and two on contractility (n = 62). The uterine artery pulsatility index was significantly lower in women with fibroids compared to controls (MD -0.63, 95% CI -0.91 to -0.36; <i>I</i> <sup>2</sup> = 91.98%), with greater reductions observed in premenopausal, non-hormonally treated, and symptomatic women. The resistance index also decreased (-0.09, 95% CI -0.15 to -0.03; <i>I</i> <sup>2</sup> = 95.86%), showing similar patterns across subgroups. Time-averaged maximum velocity was higher in the fibroid group (+18.46, 95% CI +5.54 to +31.37; <i>I</i> <sup>2</sup> = 93.64%), particularly in premenopausal and symptomatic cases. Elastography showed increased myometrial stiffness in uterine fibroids compared to controls, with a higher elastic modulus (+35.58 kPa, 95% CI +24.
研究问题:有子宫肌瘤的女性和没有子宫肌瘤病理的女性在子宫功能决定因素上有区别吗?总结回答:与对照组相比,子宫肌瘤患者一贯表现出子宫功能决定因素的改变,其特征是灌注增加、僵硬升高和收缩能力受损。已知情况:未怀孕子宫的功能决定因素在很大程度上仍未被探索和低估。子宫肌瘤作为一种定义明确的形态肌瘤病理,为理解子宫功能提供了独特的模型。研究设计规模持续时间:本系统综述和荟萃分析纳入了截至2024年12月20日在PubMed、Embase和Scopus数据库中检索的英文原创文章。该搜索策略将与子宫肌瘤相关的术语与描述子宫功能参数的术语(如子宫血管性、僵硬性和收缩性)以及诊断方法(包括多普勒超声、弹性成像和磁共振成像)结合起来。参与者/材料设置方法:采用预先确定的人群、干预(调查测量)、比较物、结果、研究类型(PICOS)标准,选择评估子宫肌瘤非妊娠妇女和无子宫肌瘤病理对照者子宫功能定量决定因素的观察性研究。结果包括子宫功能的定量测量,如血管化(子宫动脉多普勒指数)、刚度(弹性图参数)和收缩性(蠕动参数)。使用纽卡斯尔-渥太华量表评估研究质量。使用随机效应模型计算连续结果的汇总估计值,以95% ci的平均差(MD)表示。亚组分析解决了潜在的混杂因素,包括绝经状态、激素治疗使用和症状严重程度。主要结果和偶然性的作用:14项研究符合纳入标准:7项关于血管化(n = 961), 5项关于僵硬(n = 342), 2项关于收缩性(n = 62)。与对照组相比,子宫肌瘤患者的子宫动脉搏动指数显著降低(MD -0.63, 95% CI -0.91至-0.36;i2 = 91.98%),绝经前、未接受激素治疗和有症状的女性的降幅更大。抗性指数也下降(-0.09,95% CI -0.15 ~ -0.03; i2 = 95.86%),在亚组间表现出相似的模式。肌瘤组的时间平均最大流速更高(+18.46,95% CI +5.54 ~ +31.37; i2 = 93.64%),尤其是绝经前和有症状的病例。弹性成像显示,与对照组相比,子宫肌瘤的肌层硬度增加,弹性模量(+35.58 kPa, 95% CI +24.94至+46.22;I 2 = 0%)和横波速度(+1.14 m/s, 95% CI +0.62至+1.65;I 2 = 0%)更高。有限的证据表明,在有症状的肌瘤中,蠕动活动减少和收缩模式改变。谨慎的局限性原因:尽管研究结果在多种子宫功能决定因素中是一致的,但相对较小的研究人群和估计的高度异质性需要谨慎的解释。研究结果的更广泛意义:与没有子宫肌瘤病理的对照组相比,患有子宫肌瘤的女性一贯表现出子宫功能决定因素的改变,突出了结构异常如何与功能改变并行。利用肌瘤作为模型,通过先进的多模式方法将结构成像与功能评估相结合,可以加深我们对子宫疾病的理解,最终提高治疗和患者护理水平。研究经费/竞争利益:本研究部分由意大利卫生部资助。资金来源在研究设计中没有作用;数据分析:对数据的收集、分析或解释;在撰写报告时;或者在决定提交文章发表时。E.S.报告Ferring、Theramex和IBSA的研究经费和IBSA、Gedeon-Richter和Sandoz的讲座酬金。他是人类生殖开放杂志的主编。P.V.作为《子宫内膜异位症和子宫疾病杂志》的联合主编获得荣誉。其余作者没有任何利益冲突需要披露。注册编号:普洛斯彼罗ID: crd42024619633 -注册于2024年12月10日。
{"title":"Decoding uterine (dys)function in fibroids through multimodal assessment of functional determinants: a systematic review and meta-analysis.","authors":"Noemi Salmeri, Edgardo Somigliana, Alexander Fiore, Davide Marinello, Benedetta Maizza, Francesca Filippi, Paola Viganò, Fabio Parazzini","doi":"10.1093/hropen/hoaf060","DOIUrl":"10.1093/hropen/hoaf060","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Is there a difference in uterine functional determinants between women with fibroids and women without myometrial pathology?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Women with uterine fibroids consistently exhibit altered uterine functional determinants compared to controls, characterized by increased perfusion, elevated stiffness, and impaired contractility.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;The functional determinants of the non-pregnant uterus remain largely unexplored and underreported. Uterine fibroids, as a well-defined morphological myometrial pathology, offer a unique model for understanding uterine functionality.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;This systematic review and meta-analysis included original articles published in English and indexed in PubMed, Embase, and Scopus databases up to 20 December 2024. The search strategy combined terms related to uterine fibroids with those describing uterine functional parameters (e.g. uterine vascularity, stiffness, and contractility), together with diagnostic methods (including Doppler ultrasound, elastography, and magnetic resonance imaging).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;Observational studies evaluating quantitative uterine functional determinants in non-pregnant women with fibroids and controls without myometrial pathology were selected using predefined Population, Intervention (Investigated measure), Comparator, Outcome(s), Study type (PICOS) criteria. Outcomes included quantitative measures of uterine functionality such as vascularization (uterine artery Doppler indices), stiffness (elastography parameters), and contractility (peristalsis parameters). Study quality was evaluated using the Newcastle-Ottawa Scale. Pooled estimates for continuous outcomes were calculated using random-effects models, expressed as mean difference (MD) with 95% CIs. Subgroup analyses addressed potential confounders, including menopausal status, hormonal therapy use, and symptom severity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Fourteen studies met the inclusion criteria: seven on vascularization (n = 961), five on stiffness (n = 342), and two on contractility (n = 62). The uterine artery pulsatility index was significantly lower in women with fibroids compared to controls (MD -0.63, 95% CI -0.91 to -0.36; &lt;i&gt;I&lt;/i&gt; &lt;sup&gt;2&lt;/sup&gt; = 91.98%), with greater reductions observed in premenopausal, non-hormonally treated, and symptomatic women. The resistance index also decreased (-0.09, 95% CI -0.15 to -0.03; &lt;i&gt;I&lt;/i&gt; &lt;sup&gt;2&lt;/sup&gt; = 95.86%), showing similar patterns across subgroups. Time-averaged maximum velocity was higher in the fibroid group (+18.46, 95% CI +5.54 to +31.37; &lt;i&gt;I&lt;/i&gt; &lt;sup&gt;2&lt;/sup&gt; = 93.64%), particularly in premenopausal and symptomatic cases. Elastography showed increased myometrial stiffness in uterine fibroids compared to controls, with a higher elastic modulus (+35.58 kPa, 95% CI +24.","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 4","pages":"hoaf060"},"PeriodicalIF":11.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12527344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145310004","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
Life's Essential 8 score and its association with sperm quality parameters in reproductive-aged men: evidence from the Led-Fertyl cohort. 生命基本8分及其与育龄男性精子质量参数的关系:来自lead - fertyl队列的证据。
IF 11.1 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-09-18 eCollection Date: 2025-01-01 DOI: 10.1093/hropen/hoaf059
Estefanía Davila-Cordova, Albert Salas-Huetos, María Fernández de la Puente, Carla Ramos-Rodríguez, María Ángeles Martínez, Silvia Canudas, Antoni Palau-Galindo, Cristina Mestres-Solà, José María Manzanares-Errazu, Elena Sánchez-Resino, Michelle M Murphy, Jordi Salas-Salvadó, Nancy Babio

Study question: Is Life's Essential 8 (LE8) score associated with sperm quality parameters in healthy reproductive-aged men?

Summary answer: Higher LE8 score adherence is positively associated with total sperm count, sperm concentration, total motility, and progressive motility.

What is known already: Several lifestyle and cardiovascular risk factors may affect sperm quality, but there is limited scientific evidence in men.

Study design size duration: A cross-sectional analysis in the context of the Led-Fertyl (Lifestyle and Environmental Determinants of Seminogram and Other Male Fertility-Related Parameters) study was conducted.

Participants/materials setting methods: A total of 223 young men aged 18-40 years were recruited between February 2021 and December 2024 in Reus (Catalonia, Spain). The AHA-LE8 ideal cardiovascular health (CVH) score (ranging from 0 to 100) was calculated as the means of eight CVH metrics and was considered as exposure. This score is based on four health behaviors (healthy diet, adequate physical activity, avoidance of nicotine, and healthy sleep) and four health factors (healthy weight, and healthy levels of blood lipids, blood glucose, and blood pressure). Conventional sperm quality parameters (count, concentration, vitality, total and progressive motility, and normal sperm morphology) were considered the main outcomes. Adherence to the LE8 score was categorized into tertiles using the lowest tertile as the reference (T1). All regression models were adjusted for several potential confounders: age (years), education (high school or less, college or higher education), monthly income (<2000 euros and ≥2000 euros), and sexual abstinence (days).

Main results and the role of chance: Compared with those in the lowest tertile, men in the highest tertile of the LE8 score had higher sperm concentration (β = 1.11; 95% CI: 0.12, 2.09), total motility (β = 6.05; 95% CI: 0.44, 11.65), and progressive motility (β = 5.84; 95% CI: 0.19, 11.48). In the continuous analysis, each 10-point increase in the LE8 score was positively associated with total sperm count (β = 0.88; 95% CI: 0.13, 1.63), sperm concentration (β = 0.45; 95% CI: 0.03, 0.86), total (β = 2.91; 95% CI: 0.56, 5.26), and progressive motility (β = 3.00; 95% CI: 0.63, 5.36). Compared with participants in the lowest tertile of the LE8 score, those in the highest tertile were 68% less likely to have an abnormal seminogram, according to the World Health Organization (2010) thresholds (OR: 0.32; 95% CI: 0.15, 0.67).

Limitations reasons for caution: Due to the cross-sectional design, a cause-effect relationship cannot be established. It is also not possible to generalize these results to other populations.

Wider implications of the findings: Our findings

研究问题:健康育龄男性的生命基本8 (LE8)评分与精子质量参数相关吗?总结回答:较高的LE8评分依从性与总精子数、精子浓度、总活动力和进行性活动力呈正相关。已知情况:一些生活方式和心血管风险因素可能会影响精子质量,但在男性身上的科学证据有限。研究设计规模持续时间:在Led-Fertyl(生活方式和环境因素对精子图和其他男性生育相关参数的影响)研究的背景下进行了横断面分析。参与者/材料设置方法:2021年2月至2024年12月在Reus(加泰罗尼亚,西班牙)招募了223名年龄在18-40岁之间的年轻人。AHA-LE8理想心血管健康(CVH)评分(范围从0到100)被计算为8个CVH指标的平均值,并被认为是暴露。这个分数是基于四种健康行为(健康的饮食、充足的体育活动、避免尼古丁和健康的睡眠)和四个健康因素(健康的体重、健康的血脂、血糖和血压水平)。常规精子质量参数(数量、浓度、活力、总活力和进展活力以及正常精子形态)被认为是主要结果。以最低分位数作为参考(T1),对LE8评分的依从性进行分类。所有回归模型都针对几个潜在的混杂因素进行了调整:年龄(岁)、教育程度(高中或以下、大学或高等教育)、月收入(主要结果和机会的作用:与最低分的男性相比,LE8得分最高分的男性具有更高的精子浓度(β = 1.11; 95% CI: 0.12, 2.09)、总运动性(β = 6.05; 95% CI: 0.44, 11.65)和渐进运动性(β = 5.84; 95% CI: 0.19, 11.48)。在连续分析中,LE8评分每增加10分,与总精子数(β = 0.88; 95% CI: 0.13, 1.63)、精子浓度(β = 0.45; 95% CI: 0.03, 0.86)、总精子数(β = 2.91; 95% CI: 0.56, 5.26)和进行活力(β = 3.00; 95% CI: 0.63, 5.36)呈正相关。根据世界卫生组织(2010)的阈值(OR: 0.32; 95% CI: 0.15, 0.67),与LE8得分最低分位数的参与者相比,最高分位数的参与者出现精原图异常的可能性要低68%。局限性:由于采用横断面设计,不能建立因果关系。也不可能将这些结果推广到其他人群。研究结果的更广泛含义:我们的研究结果表明,LE8评分与总精子数、精子浓度、总活动力和进行性活动力之间存在正相关。此外,在育龄健康男性中,较高的LE8评分与较低的精子异常几率相关。研究资金/竞争利益:leader - fertyl研究由西班牙政府的官方生物医学研究资助机构,Salud Carlos III研究所(ISCIII),通过Fondo de Investigacion para la Salud (FIS),欧盟ERDF/ESF, 'A way to make Europe'/'Investing in your future' [PI21/01447]和Diputació de Tarragona (2021/11-No.Exp.)提供支持。8004330008-2021-0022642)。J.S.-S。是由ICREA学术项目支持的杰出高级研究员。E.D.-C。获得了来自西班牙卫生部ISCIII的Acción estrat )计划(AES)的博士预科证书(PFIS FI22/00018)。所有作者均无利益冲突需要申报。试验注册号:无。
{"title":"Life's Essential 8 score and its association with sperm quality parameters in reproductive-aged men: evidence from the Led-Fertyl cohort.","authors":"Estefanía Davila-Cordova, Albert Salas-Huetos, María Fernández de la Puente, Carla Ramos-Rodríguez, María Ángeles Martínez, Silvia Canudas, Antoni Palau-Galindo, Cristina Mestres-Solà, José María Manzanares-Errazu, Elena Sánchez-Resino, Michelle M Murphy, Jordi Salas-Salvadó, Nancy Babio","doi":"10.1093/hropen/hoaf059","DOIUrl":"10.1093/hropen/hoaf059","url":null,"abstract":"<p><strong>Study question: </strong>Is Life's Essential 8 (LE8) score associated with sperm quality parameters in healthy reproductive-aged men?</p><p><strong>Summary answer: </strong>Higher LE8 score adherence is positively associated with total sperm count, sperm concentration, total motility, and progressive motility.</p><p><strong>What is known already: </strong>Several lifestyle and cardiovascular risk factors may affect sperm quality, but there is limited scientific evidence in men.</p><p><strong>Study design size duration: </strong>A cross-sectional analysis in the context of the Led-Fertyl (Lifestyle and Environmental Determinants of Seminogram and Other Male Fertility-Related Parameters) study was conducted.</p><p><strong>Participants/materials setting methods: </strong>A total of 223 young men aged 18-40 years were recruited between February 2021 and December 2024 in Reus (Catalonia, Spain). The AHA-LE8 ideal cardiovascular health (CVH) score (ranging from 0 to 100) was calculated as the means of eight CVH metrics and was considered as exposure. This score is based on four health behaviors (healthy diet, adequate physical activity, avoidance of nicotine, and healthy sleep) and four health factors (healthy weight, and healthy levels of blood lipids, blood glucose, and blood pressure). Conventional sperm quality parameters (count, concentration, vitality, total and progressive motility, and normal sperm morphology) were considered the main outcomes. Adherence to the LE8 score was categorized into tertiles using the lowest tertile as the reference (T1). All regression models were adjusted for several potential confounders: age (years), education (high school or less, college or higher education), monthly income (<2000 euros and ≥2000 euros), and sexual abstinence (days).</p><p><strong>Main results and the role of chance: </strong>Compared with those in the lowest tertile, men in the highest tertile of the LE8 score had higher sperm concentration (<i>β</i> = 1.11; 95% CI: 0.12, 2.09), total motility (<i>β</i> = 6.05; 95% CI: 0.44, 11.65), and progressive motility (<i>β</i> = 5.84; 95% CI: 0.19, 11.48). In the continuous analysis, each 10-point increase in the LE8 score was positively associated with total sperm count (<i>β</i> = 0.88; 95% CI: 0.13, 1.63), sperm concentration (<i>β</i> = 0.45; 95% CI: 0.03, 0.86), total (<i>β</i> = 2.91; 95% CI: 0.56, 5.26), and progressive motility (<i>β</i> = 3.00; 95% CI: 0.63, 5.36). Compared with participants in the lowest tertile of the LE8 score, those in the highest tertile were 68% less likely to have an abnormal seminogram, according to the World Health Organization (2010) thresholds (OR: 0.32; 95% CI: 0.15, 0.67).</p><p><strong>Limitations reasons for caution: </strong>Due to the cross-sectional design, a cause-effect relationship cannot be established. It is also not possible to generalize these results to other populations.</p><p><strong>Wider implications of the findings: </strong>Our findings ","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 4","pages":"hoaf059"},"PeriodicalIF":11.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253810","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
Live birth rates are unrelated to sex-steroid levels on ET day in a dydrogesterone-based 'programmed-ovulatory FET' protocol: a multi-centric prospective cohort study. 在以地屈孕酮为基础的“计划性排卵FET”方案中,活产率与ET当天的性类固醇水平无关:一项多中心前瞻性队列研究。
IF 11.1 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-09-15 eCollection Date: 2025-01-01 DOI: 10.1093/hropen/hoaf058
Tanja K Eggersmann, Noemi Hamala, Alexander R Hiller, Marion Depenbusch, Askan Schultze-Mosgau, Philippos Edimiris, Dunja Baston-Büst, Alexandra P Bielfeld, Jan-Steffen Kruessel, Sören von Otte, Wiebe Junkers, Sascha Tauchert, Reinhard Vonthein, Georg Griesinger

Study question: What are the effects of three-times-a-day 10 mg oral dydrogesterone (DYD), initiated in the late follicular phase of natural menstrual cycles to induce endometrial receptivity for frozen-thawed embryo transfer (FET), on progesterone levels, indicative of ovulation on the day of FET, and how are levels of DYD, 20α-dihydrodydrogesterone (DHD), progesterone (P), and estradiol (E2) on the day of FET associated with clinical outcomes?

Summary answer: Late follicular phase initiation of oral 30 mg DYD is compatible with progesterone levels indicative of ovulation in 98% of cases, and DYD, DHD, P, and E2 blood levels on the day of FET do not show a consistent relationship with live birth achievement, whether evaluated in isolation or interaction.

What is known already: HRT regimens for FET have come under scrutiny due to: (i) the risk of insufficient progesterone exposure with conventional dosing schemes, and (ii) maternal and fetal risks associated with the iatrogenic absence of a corpus luteum. Oral DYD 10 mg three-times-a-day (tid) is considered unlikely to interfere with ovulation or corpus luteum formation and does not exhibit cross-reactivity with progesterone in ELISA. Therefore, it can be used to induce endometrial receptivity (i.e. to schedule the timing of FET in a natural cycle) and provide luteal phase support (LPS) while allowing ovulation to occur independently of the implantation window and enabling the monitoring of endogenous progesterone serum levels.

Study design size duration: Nested within a multi-centric, prospective, clinical cohort study (NCT03507673), 559 normally cycling women from the routine care population who underwent FET in a spontaneous menstrual cycle (12/2021-8/2023) had DYD, DHD, P, and E2 levels on day of FET measured by high-performance liquid chromatography/tandem mass spectroscopy (HPLC/MS/MS) or commercially available electrochemiluminescence immunoassay (ECLIA).

Participants/materials setting methods: Starting from cycle day 10, women underwent endocrine (E2, LH, and P) and sonographic monitoring until the following criteria were ideally met: a leading follicle ≥16 mm, endometrial thickness ≥6 mm, and E2 ≥ 180 pg/ml. At this point, physicians could initiate oral DYD 10 mg (tid) or, if there was no LH rise in serum, postpone initiation within 2 days of monitoring to align with patient and/or centre preferences (e.g. avoiding weekends). FET for Day 2-Day 5 embryos was performed on Day 3-6 of DYD intake.

Main results and the role of chance: DYD and DHD plasma levels on Day 3-6 of intake replicate previous findings. In FET with Day 4 or 5 embryos, serum P levels indicated ovulation in 98.1% (>1.5 ng/ml) and 95.4% (>3.0 ng/ml) of cases and levels were higher (ratio of geometric means 2.88, 95% CI 2.48-3.35) than in FET with Day 2 or 3 embryos. Progesterone levels on da

研究问题:在自然月经周期的卵泡晚期开始口服地孕酮(DYD),每天3次,每次10毫克,以诱导子宫内膜接受冻融胚胎移植(FET),对FET当天排卵指标黄体酮水平的影响是什么?以及FET当天的DYD、20α-二氢地孕酮(DHD)、黄体酮(P)和雌二醇(E2)水平如何与临床结果相关?总结性回答:卵泡晚期开始口服30mg DYD与98%的病例显示排卵的孕酮水平一致,FET当天的DYD、DHD、P和E2血液水平与活产成就没有一致的关系,无论是单独评估还是相互作用评估。已知情况:FET的HRT方案已经受到审查,因为:(i)传统剂量方案的黄体酮暴露不足的风险,以及(ii)与黄体的医源性缺失相关的母婴风险。口服DYD 10mg,每日三次(tid)被认为不太可能干扰排卵或黄体形成,并且在ELISA中不表现出与黄体酮的交叉反应性。因此,它可以用于诱导子宫内膜容受性(即在自然周期中安排FET的时间)和提供黄体期支持(LPS),同时允许排卵独立于植入窗口发生,并能够监测内源性黄体酮血清水平。研究设计规模持续时间:在一项多中心、前瞻性临床队列研究(NCT03507673)中,通过高效液相色谱/串联质谱(HPLC/MS/MS)或市售电化学发光免疫分析法(ECLIA)测量559名常规护理人群中在自然月经周期(12/2021-8/2023)接受FET的正常周期女性在FET当天的DYD、DHD、P和E2水平。受试者/材料设置方法:从月经周期第10天开始,妇女接受内分泌(E2, LH和P)和超声监测,直到理想地满足以下标准:前导卵泡≥16mm,子宫内膜厚度≥6mm, E2≥180pg /ml。此时,医生可以开始口服DYD 10mg (tid),或者,如果血清LH没有升高,根据患者和/或中心的偏好(例如避免周末),在监测的2天内推迟开始。第2- 5天胚胎的FET在DYD摄入第3-6天进行。主要结果和偶发因素的作用:摄入后第3-6天的DYD和DHD血浆水平重复了先前的研究结果。胚胎发育第4天或第5天的FET患者血清P水平显示排卵率为98.1% (>1.5 ng/ml)和95.4% (>3.0 ng/ml),且P水平高于胚胎发育第2天或第3天的FET患者(几何平均比值2.88,95% CI 2.48-3.35)。天孕酮水平的场效应晶体管无关(几何比率意味着1.13,95%可信区间0.95 - -1.34)卵泡大小(≤16毫米vs > 16毫米),只略高(几何比率意味着1.36,95%可信区间1.19 - -1.56)的血清LH水平≥12.6 IU / l和第25百分位)激素水平(DYD RD -5.3%, 95%可信区间-14.0到3.2,P = 0.227; DHD RD -4.0%, 95%可信区间-14.6到6.0,P = 0.428;孕激素RD 2.9%, 95%可信区间-7.0到12.3,P = 0.597; E2 RD -3.3%, 95%可信区间-12.2到5.3,P = 0.487)。这些发现在整个激素值范围内得到了logistic回归的证实,在未调整的显著性水平0.05下,评估的激素对活产率没有相互作用。注意的局限性:所有结果仅在接受FET治疗的受试者中进行评估,而不是意向治疗。口服DYD 10mg (tid),与其他用于诱导子宫内膜容受性或LPS的黄体酮类似,可能仍会干扰LH激增、排卵和黄体期特征,需要使用真正的自然周期(NC)作为参考进行进一步的研究。研究结果的更广泛含义:我们建议将该方案称为“程序化-排卵(PO-) FET”。PO-FET方案可以安排植入窗口,允许排卵和黄体形成,提供双孕支持,并可能消除在FET当天控制性类固醇测量的需要。它可以监测黄体期和妊娠早期的黄体活动,无需注射,药物成本低。该方案需要在随机对照试验中对其他排卵期FET方案进行测试,如“NC FET”或“管理NC FET”。研究经费/竞争利益:该试验由石勒苏益格-荷尔斯泰因大学医院的机构资源资助,校园l<e:1>贝克。与血浆和血清样品处理、储存、运输以及DYD、DHD、雌二醇和黄体酮的HPLC/MS/MS和ELISA分析相关的费用由雅培产品运营公司(瑞士Allschwil)资助。 这笔资金以研究补助金的形式提供给石勒苏益格-荷尔斯泰因大学医院妇科内分泌和生殖医学系,校园l<e:1>(没有适用的补助金编号)。雅培产品运营公司没有参与研究的设计、实施、数据收集、统计分析、数据解释、手稿准备或决定是否将文章提交发表。T.K.E.披露fering的酬金;Merck、Ferring、Theramex和Gedeon-Richter的差旅支持;在提交的工作之外,从Arthrex和Besins Healthcare接收设备/材料(给机构)。除了提交的工作外,N.H.还收到了Gedeon-Richter、Ferring和默克公司的差旅支持。除了提交的工作外,A.R.H.还收到了来自Organon的酬金和来自默克雪兰诺(Merck Serono)、Gedeon Richter和Theramex的差旅支持。在提交的工作之外,医学博士披露了默克公司的差旅支持。P.E.披露了Ferring, Theramex和Gedeon Richter的酬金;以及在提交的工作之外,由默克、菲灵、Theramex、Gedeon Richter和默沙东提供的差旅支持。A.P.B.披露了来自默克、Theramex、Gedeon Richter和Ferring的酬金和旅行支持;在提交的工作之外,参与fering和默克的数据安全监测委员会或咨询委员会。A.S.-M。, D.B.-B。, j - s - k, s - v - o, w - j, s - t, r - v声明没有利益冲突。G.G.披露了在提交作品之外来自默克、奥肯、Ferring、Theramex、Gedeon-Richter、雅培、Biosilu、repdwissen、Obseva、PregLem、Guerbet、Cooper、Igyxos、OxoLife和ReproNovo的咨询费和酬金,以及在提交作品之外来自默克、奥肯、Ferring、Theramex、Gedeon-Richter和雅培的差旅支持。没有与提交的工作直接相关的冲突。试验注册号:NCT03507673。
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引用次数: 0
Bone mineralization in children aged 7-10 years born after ART with frozen and fresh embryo transfer. 冷冻和新鲜胚胎移植ART后出生的7-10岁儿童骨矿化。
IF 11.1 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-09-11 eCollection Date: 2025-01-01 DOI: 10.1093/hropen/hoaf055
Elisabeth Waldemar Grønlund, Anna Sophie Lebech Kjaer, Louise Laub Asserhøj, Ikram Mizrak, Tine Dahlsgaard Clausen, Per Laub Madsen, Anja Pinborg, Rikke Beck Jensen
<p><strong>Study question: </strong>Does height-adjusted bone mineral content (BMC) at 7-10 years of age differ between children conceived after ART with frozen embryo transfer (FET) compared to children conceived after ART with fresh embryo transfer (fresh-ET) or naturally conceived (NC) children?</p><p><strong>Summary answer: </strong>Children conceived after FET had an increased BMC corrected for height compared with fresh-ET and NC when adjusted for confounders, a difference primarily mediated by the higher birthweight (BW) found in children conceived after FET compared with fresh-ET and NC.</p><p><strong>What is known already: </strong>Children conceived after ART with FET have a higher BW compared to NC children, while the opposite association is known for fresh-ET. In NC children, BW is positively associated with BMC and bone mineral density (BMD), but bone health in children born after ART is scarcely explored with inconsistent results.</p><p><strong>Study design size duration: </strong>This study was a retrospective cohort study as part of the 'Health in Childhood following Assisted Reproductive Technology' (HiCART) cohort, consisting of 606 singletons (292 boys), conceived after FET (n = 200), fresh-ET (n = 203), and NC (n = 203) born from November 2009 to December 2013. The children were 7-10 years old when clinically examined, and the study was conducted from January 2019 to September 2021.</p><p><strong>Participants/materials setting methods: </strong>Children were identified through the Danish Medical Birth Registry and Danish IVF Registry. These registries were also used to collect information regarding ART treatment, pregnancy, and delivery. The clinical examination involved anthropometric measurements, pubertal staging, fasting blood samples, and a whole-body dual-energy x-ray absorptiometry (DXA) scan. Both parents completed a questionnaire on background information regarding themselves and their child. The three groups were compared pairwise using univariate linear regression, and possible confounders and mediators were adjusted for using multiple linear regression analysis.</p><p><strong>Main results and the role of chance: </strong>Crude values of BMC corrected for height did not differ between children born after FET, fresh-ET, or NC. When adjusted for relevant confounders, children born after FET had a statistically significant higher BMC corrected for height compared with both fresh-ET and NC. After further adjustment for BW SD score, the differences in BMC corrected for height disappeared, and no statistically significant differences in BMC corrected for height between any of the three groups were found. Factors potentially affecting bone mineralization, such as calcium, parathyroid hormone (PTH), insulin-like growth factor-1 (IGF-1), lean mass, and physical activity in childhood, did not differ between the three groups.</p><p><strong>Limitations reasons for caution: </strong>All relevant confounders were adjusted for, al
研究问题:在7-10岁时,接受ART合并冷冻胚胎移植(FET)的儿童与接受ART合并新鲜胚胎移植(fresh- et)或自然受孕(NC)的儿童相比,身高调整骨矿物质含量(BMC)有差异吗?摘要回答:经混杂因素调整后,FET后怀孕的儿童与新鲜et和NC相比,身高校正后的BMC增加,差异主要是由FET后怀孕的儿童与新鲜et和NC相比的出生体重(BW)较高介导的。已知情况:与未接受ART治疗的儿童相比,接受FET治疗后出生的儿童体重更高,而未接受FET治疗的儿童体重则相反。在NC儿童中,体重与BMC和骨密度(BMD)呈正相关,但对ART后出生儿童的骨骼健康几乎没有研究,结果不一致。研究设计规模持续时间:本研究是一项回顾性队列研究,作为“辅助生殖技术后儿童健康”(HiCART)队列的一部分,包括606名单胎(292名男孩),分别是2009年11月至2013年12月出生的FET (n = 200)、新鲜et (n = 203)和NC (n = 203)。临床检查时,这些儿童的年龄为7-10岁,研究于2019年1月至2021年9月进行。参与者/材料设置方法:通过丹麦医学出生登记处和丹麦试管婴儿登记处确定儿童。这些登记还用于收集有关抗逆转录病毒治疗、妊娠和分娩的信息。临床检查包括人体测量、青春期分期、空腹血液样本和全身双能x线吸收仪(DXA)扫描。父母双方都完成了一份关于他们自己和孩子的背景信息的调查问卷。使用单变量线性回归对三组进行两两比较,并使用多元线性回归分析调整可能的混杂因素和中介因素。主要结果和机会的作用:在FET,新鲜et或NC后出生的儿童中,身高校正的BMC粗值没有差异。当对相关混杂因素进行调整后,与新鲜et和NC相比,FET后出生的儿童的身高校正BMC具有统计学意义上的更高。进一步调整BW SD评分后,身高校正BMC的差异消失,三组之间身高校正BMC的差异无统计学意义。潜在影响骨矿化的因素,如钙、甲状旁腺激素(PTH)、胰岛素样生长因子-1 (IGF-1)、瘦体重和儿童时期的体育活动,在三组之间没有差异。注意的局限性:所有相关的混杂因素都进行了调整,尽管不孕的原因无法获得,因此存在残留混杂的风险。使用家长问卷调查儿童的身体活动水平设置了信息偏差的风险。研究结果的更广泛意义:与新鲜et和NC后怀孕的儿童相比,FET后怀孕的儿童体重增加与7-10岁时身高校正BMC增加有关。需要对FET后的妊娠和新生儿进行纵向研究,以探索体重增加的原因及其对长期骨骼健康的可能影响。研究经费/竞争利益:本研究由诺和诺德基金会(批准号:NNF18OC0034092, NFF19OC0054340)和Rigshospitalet研究基金会资助。ap已获得Gedeon Richter、Ferring Pharmaceuticals、Merck和Cryos的资助;Gedeon Richter、Ferring Pharmaceuticals、Merck、Cryos和IBSA的咨询费;Gedeon Richter、Ferring Pharmaceuticals、Merck和Organon的演讲费;以及Gedeon Richter的旅行补助其余作者声明无利益冲突。试验注册号:ClinicalTrials.gov标识符:NCT03719703。
{"title":"Bone mineralization in children aged 7-10 years born after ART with frozen and fresh embryo transfer.","authors":"Elisabeth Waldemar Grønlund, Anna Sophie Lebech Kjaer, Louise Laub Asserhøj, Ikram Mizrak, Tine Dahlsgaard Clausen, Per Laub Madsen, Anja Pinborg, Rikke Beck Jensen","doi":"10.1093/hropen/hoaf055","DOIUrl":"10.1093/hropen/hoaf055","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Does height-adjusted bone mineral content (BMC) at 7-10 years of age differ between children conceived after ART with frozen embryo transfer (FET) compared to children conceived after ART with fresh embryo transfer (fresh-ET) or naturally conceived (NC) children?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Children conceived after FET had an increased BMC corrected for height compared with fresh-ET and NC when adjusted for confounders, a difference primarily mediated by the higher birthweight (BW) found in children conceived after FET compared with fresh-ET and NC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Children conceived after ART with FET have a higher BW compared to NC children, while the opposite association is known for fresh-ET. In NC children, BW is positively associated with BMC and bone mineral density (BMD), but bone health in children born after ART is scarcely explored with inconsistent results.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;This study was a retrospective cohort study as part of the 'Health in Childhood following Assisted Reproductive Technology' (HiCART) cohort, consisting of 606 singletons (292 boys), conceived after FET (n = 200), fresh-ET (n = 203), and NC (n = 203) born from November 2009 to December 2013. The children were 7-10 years old when clinically examined, and the study was conducted from January 2019 to September 2021.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;Children were identified through the Danish Medical Birth Registry and Danish IVF Registry. These registries were also used to collect information regarding ART treatment, pregnancy, and delivery. The clinical examination involved anthropometric measurements, pubertal staging, fasting blood samples, and a whole-body dual-energy x-ray absorptiometry (DXA) scan. Both parents completed a questionnaire on background information regarding themselves and their child. The three groups were compared pairwise using univariate linear regression, and possible confounders and mediators were adjusted for using multiple linear regression analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Crude values of BMC corrected for height did not differ between children born after FET, fresh-ET, or NC. When adjusted for relevant confounders, children born after FET had a statistically significant higher BMC corrected for height compared with both fresh-ET and NC. After further adjustment for BW SD score, the differences in BMC corrected for height disappeared, and no statistically significant differences in BMC corrected for height between any of the three groups were found. Factors potentially affecting bone mineralization, such as calcium, parathyroid hormone (PTH), insulin-like growth factor-1 (IGF-1), lean mass, and physical activity in childhood, did not differ between the three groups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations reasons for caution: &lt;/strong&gt;All relevant confounders were adjusted for, al","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 4","pages":"hoaf055"},"PeriodicalIF":11.1,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145132917","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
Levothyroxine supplementation and pregnancy outcomes in women with thyroid disorders: an umbrella review of systematic reviews and meta-analyses of randomized controlled trials. 甲状腺疾病妇女补充左旋甲状腺素与妊娠结局:随机对照试验的系统评价和荟萃分析综述
IF 11.1 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-09-08 eCollection Date: 2025-01-01 DOI: 10.1093/hropen/hoaf036
Jing Wang, Jiashu Li, Jing Zhang, Aihua Liu, Wanyu Yang, Xiaodan Zhai, Weiping Teng, Yongze Li, Zhongyan Shan
<p><strong>Study question: </strong>Does levothyroxine (LT4) treatment reduce adverse pregnancy outcomes in pregnant women with thyroid dysfunction?</p><p><strong>Summary answer: </strong>LT4 treatment significantly reduces the risks of pregnancy loss, preterm delivery, and gestational hypertension, with no significant impacts on rates of live birth, placental abruption, or gestational diabetes.</p><p><strong>What is known already: </strong>Multiple meta-analyses have examined the impact of LT4 on pregnancy outcomes, but quantitative confidence assessments are still lacking. Thus, an umbrella review is needed to systematically synthesize and assess the quality of this evidence.</p><p><strong>Study design size duration: </strong>This umbrella review of systematic reviews and meta-analyses used PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews. Searches included studies published in English or Chinese up to 20 March 2025.</p><p><strong>Participants/materials setting methods: </strong>Included studies were systematic reviews or meta-analyses of randomized controlled trials assessing the effects of LT4 on pregnancy outcomes in women with subclinical hypothyroidism (SCH) or thyroid peroxidase antibody (TPOAb) positivity. A set of 24 associations across six pregnancy outcomes were analyzed: pregnancy loss, preterm delivery, live birth, placental abruption, gestational hypertension, and gestational diabetes. Methodological quality was assessed using AMSTAR 1, and evidence quality was graded using GRADE. Sensitivity analyses were conducted to confirm robustness.</p><p><strong>Main results and the role of chance: </strong>Eleven meta-analyses were included. High-quality evidence showed that LT4 treatment reduced the risks of pregnancy loss (RR = 0.43; class III evidence), preterm delivery (RR = 0.56; class III evidence), and gestational hypertension (RR = 0.63; class IV evidence). Moderate-to-low-quality evidence indicated no significant impact on rates of live birth, placental abruption, or gestational diabetes. Of the 24 associations, 22 were rated as high confidence and two as medium confidence based on AMSTAR 1. Sensitivity analyses confirmed the robustness of the findings, but treatment effects varied according to the study population, treatment timing, and method. For pregnancy loss and preterm delivery outcomes, the risk was significantly reduced only when LT4 treatment was initiated in early pregnancy (pregnancy loss: RR = 0.60, <i>P</i> = 0.03; RR = 0.59, <i>P</i> = 0.003; preterm labor: RR = 0.58, <i>P </i>< 0.0001; RR = 0.46, <i>P</i> < 0.00001). Additionally, women with TSH levels greater than 4.0 mU/l derived greater benefits from LT4 treatment compared to those with TSH levels between 2.5 and 4.0 mU/l.</p><p><strong>Limitations reasons for caution: </strong>Limitations include small sample sizes, potential biases (selection and reporting), and language restrictions to English and Chinese studies, which may affec
研究问题:左旋甲状腺素(LT4)治疗是否能减少甲状腺功能障碍孕妇的不良妊娠结局?总结回答:LT4治疗可显著降低流产、早产和妊娠期高血压的风险,对活产、胎盘早剥或妊娠期糖尿病的发生率无显著影响。已知情况:多项荟萃分析已经研究了LT4对妊娠结局的影响,但仍然缺乏定量的信心评估。因此,有必要对这些证据的质量进行系统的综合和评估。研究设计规模持续时间:本综述使用PubMed、Embase、Web of Science和Cochrane系统综述数据库对系统综述和荟萃分析进行综述。检索包括截至2025年3月20日以英文或中文发表的研究。参与者/材料设置方法:纳入的研究是评估LT4对亚临床甲状腺功能减退症(SCH)或甲状腺过氧化物酶抗体(TPOAb)阳性妇女妊娠结局影响的随机对照试验的系统评价或荟萃分析。研究人员分析了6种妊娠结局的24项关联:流产、早产、活产、胎盘早剥、妊娠期高血压和妊娠期糖尿病。采用AMSTAR 1评估方法学质量,采用GRADE对证据质量进行分级。进行敏感性分析以确认稳健性。主要结果和偶然性的作用:包括11项荟萃分析。高质量证据显示,LT4治疗降低了妊娠丢失(RR = 0.43, III类证据)、早产(RR = 0.56, III类证据)和妊娠期高血压(RR = 0.63, IV类证据)的风险。中等到低质量的证据表明,对活产率、胎盘早剥或妊娠糖尿病没有显著影响。在24个协会中,根据AMSTAR 1, 22个被评为高可信度,2个被评为中等可信度。敏感性分析证实了研究结果的稳健性,但治疗效果因研究人群、治疗时间和方法而异。对于妊娠丢失和早产结局,只有在妊娠早期开始LT4治疗时,风险才会显著降低(妊娠丢失:RR = 0.60, P = 0.03; RR = 0.59, P = 0.003;早产:RR = 0.58, P)谨慎的局限性原因:局限性包括样本量小,潜在的偏差(选择和报告),以及对中英文研究的语言限制,这可能会影响推广。研究结果的更广泛意义:通过整合高质量的证据,本研究证实LT4可以降低甲状腺功能障碍孕妇的妊娠丢失和早产风险,支持其在特定人群的临床应用,如TPOAb阳性或TSH > 4.0 mU/l的SCH患者,并警告过度治疗的风险。本研究结果为临床精准干预提供了依据。未来的研究应通过标准化的大型研究来解决异质性问题,明确剂量阈值,评估LT4对母婴的长期健康影响,进一步完善指南,优化风险分层管理。研究经费/利益竞争:国家重点研发计划项目(批准号:2023YFC2508300、2023YFC2508303、2023YFC2508305)、国家科技重大专项项目(批准号:2024ZD0533403)、国家自然科学基金项目(批准号:82100831、81570709、82470826)资助。所有作者都声明没有利益冲突。注册号:CRD42024586105。
{"title":"Levothyroxine supplementation and pregnancy outcomes in women with thyroid disorders: an umbrella review of systematic reviews and meta-analyses of randomized controlled trials.","authors":"Jing Wang, Jiashu Li, Jing Zhang, Aihua Liu, Wanyu Yang, Xiaodan Zhai, Weiping Teng, Yongze Li, Zhongyan Shan","doi":"10.1093/hropen/hoaf036","DOIUrl":"10.1093/hropen/hoaf036","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Does levothyroxine (LT4) treatment reduce adverse pregnancy outcomes in pregnant women with thyroid dysfunction?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;LT4 treatment significantly reduces the risks of pregnancy loss, preterm delivery, and gestational hypertension, with no significant impacts on rates of live birth, placental abruption, or gestational diabetes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Multiple meta-analyses have examined the impact of LT4 on pregnancy outcomes, but quantitative confidence assessments are still lacking. Thus, an umbrella review is needed to systematically synthesize and assess the quality of this evidence.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;This umbrella review of systematic reviews and meta-analyses used PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews. Searches included studies published in English or Chinese up to 20 March 2025.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;Included studies were systematic reviews or meta-analyses of randomized controlled trials assessing the effects of LT4 on pregnancy outcomes in women with subclinical hypothyroidism (SCH) or thyroid peroxidase antibody (TPOAb) positivity. A set of 24 associations across six pregnancy outcomes were analyzed: pregnancy loss, preterm delivery, live birth, placental abruption, gestational hypertension, and gestational diabetes. Methodological quality was assessed using AMSTAR 1, and evidence quality was graded using GRADE. Sensitivity analyses were conducted to confirm robustness.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Eleven meta-analyses were included. High-quality evidence showed that LT4 treatment reduced the risks of pregnancy loss (RR = 0.43; class III evidence), preterm delivery (RR = 0.56; class III evidence), and gestational hypertension (RR = 0.63; class IV evidence). Moderate-to-low-quality evidence indicated no significant impact on rates of live birth, placental abruption, or gestational diabetes. Of the 24 associations, 22 were rated as high confidence and two as medium confidence based on AMSTAR 1. Sensitivity analyses confirmed the robustness of the findings, but treatment effects varied according to the study population, treatment timing, and method. For pregnancy loss and preterm delivery outcomes, the risk was significantly reduced only when LT4 treatment was initiated in early pregnancy (pregnancy loss: RR = 0.60, &lt;i&gt;P&lt;/i&gt; = 0.03; RR = 0.59, &lt;i&gt;P&lt;/i&gt; = 0.003; preterm labor: RR = 0.58, &lt;i&gt;P &lt;/i&gt;&lt; 0.0001; RR = 0.46, &lt;i&gt;P&lt;/i&gt; &lt; 0.00001). Additionally, women with TSH levels greater than 4.0 mU/l derived greater benefits from LT4 treatment compared to those with TSH levels between 2.5 and 4.0 mU/l.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations reasons for caution: &lt;/strong&gt;Limitations include small sample sizes, potential biases (selection and reporting), and language restrictions to English and Chinese studies, which may affec","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf036"},"PeriodicalIF":11.1,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115095","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
Generating human primordial germ cell-like cells from pluripotent stem cells: a scoping review of in vitro methods. 从多能干细胞中产生人类原始生殖细胞样细胞:体外方法的范围综述。
IF 11.1 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-09-04 eCollection Date: 2025-01-01 DOI: 10.1093/hropen/hoaf056
Madalena Vaz Santos, Ilse J de Bruin, Nina Dartée, Mathangi Lakshmipathi, Geert Hamer, Callista L Mulder, Willy M Baarends, Ans M M Van Pelt, Susana M Chuva De Sousa Lopes
<p><strong>Study question: </strong>How do the methods and outcomes of established protocols to specify human primordial germ cell-like cells (hPGCLCs) <i>in vitro</i> compare to each other?</p><p><strong>Summary answer: </strong>All analyzed protocols were successful in generating hPGCLCs, and a few were able to induce further germ cell maturation.</p><p><strong>What is known already: </strong>There are a variety of protocols for generating hPGCLCs <i>in vitro</i>, each with its own advantages and disadvantages. To date no comparison has been made, hindering the practical application of <i>in vitro</i>-derived hPGCLCs in research and the advancement toward generating mature germ cells.</p><p><strong>Study design size duration: </strong>For this scoping review, a systematic search for protocols was conducted in the databases Scopus and Web of Science, including publications since 2010. Search terms included human, differentiation/specification/induction, germ cell/oogonia/spermatogonia, and primordial.</p><p><strong>Participants/materials setting methods: </strong>Two separate authors performed the database search according to the inclusion/exclusion criteria. The data regarding the materials and methods as well as results of the included articles were extracted and organized based on protocol (cell type and culture system) and outcome.</p><p><strong>Main results and the role of chance: </strong>A systematic search revealed 32 articles describing the generation of hPGCLCs. Of these, 24 articles contained an original hPGCLC differentiation protocol and 8 articles provided an extension of a previously published protocol. The extension protocols focused either on extending hPGCLC culture or maturing hPGCLCs further. The articles were compared regarding protocol methods and differentiation outcomes. The data showed that differentiation in 2D or 3D, in the presence of bone morphogenetic protein 4 (BMP4) (or retinoic acid), activated the WNT and NODAL signaling pathways to induce hPGCLCs. Further maturation (based on gene expression) was also achieved, depending on the inclusion of subsequent differentiation steps. The 2D culture systems showed high efficiency and scalability, while the 3D culture systems were more suitable for germ cell maturation purposes. Further improvements would include a deeper assessment of epigenetic and gene expression, functional analyses, and use of multiple cell lines to reflect protocol versatility.</p><p><strong>Limitations reasons for caution: </strong>Only literature has been compared; no extensive experimental comparison or a meta-analysis was performed due to the heterogeneity in outcome measurements.</p><p><strong>Wider implications of the findings: </strong>This review offers a comparison of hPGCLC differentiation protocols and aims to aid researchers in selecting appropriate protocols and making informed modifications to the culture conditions to achieve efficient germ cell differentiation.</p><p><strong>Study fun
研究问题:在体外指定人类原始生殖细胞样细胞(hpgclc)的既定方案的方法和结果如何比较?总结回答:所有分析的方案都成功地产生了hpgclc,并且少数方案能够诱导进一步的生殖细胞成熟。已知情况:有多种体外生成hpgclc的方案,每种方案都有自己的优点和缺点。到目前为止,还没有进行比较,这阻碍了体外来源的hpgclc在研究中的实际应用和成熟生殖细胞的产生。研究设计规模持续时间:对于本次范围综述,在Scopus和Web of Science数据库中进行了系统的协议搜索,包括2010年以来的出版物。搜索词包括人类,分化/规范/诱导,生殖细胞/卵原细胞/精原细胞和原始。受试者/材料设置方法:由两位独立作者根据纳入/排除标准进行数据库检索。根据方案(细胞类型和培养系统)和结果对纳入文章的材料和方法相关数据进行提取和整理。主要结果和偶然性的作用:系统检索显示了32篇描述hpgclc产生的文章。其中,24篇文章包含原始的hPGCLC分化方案,8篇文章提供了先前发表的方案的扩展。扩展协议的重点要么是扩展hPGCLC培养,要么是进一步成熟hPGCLC。比较两篇文章的治疗方案、方法和鉴别结果。数据显示,在2D或3D分化中,在骨形态发生蛋白4 (BMP4)(或视黄酸)存在下,激活WNT和NODAL信号通路诱导hpgclc。进一步的成熟(基于基因表达)也实现了,这取决于随后的分化步骤的包含。二维培养系统具有较高的效率和可扩展性,而三维培养系统更适合生殖细胞成熟目的。进一步的改进将包括更深入的表观遗传和基因表达评估、功能分析,以及使用多细胞系来反映方案的通用性。局限性:仅比较了文献;由于结果测量的异质性,没有进行广泛的实验比较或荟萃分析。研究结果的更广泛意义:本综述提供了hPGCLC分化方案的比较,旨在帮助研究人员选择合适的方案,并对培养条件进行知情修改,以实现有效的生殖细胞分化。研究经费/竞争利益:本研究由ZonMW (PSIDER 10250022120001)和Novo Nordisk Foundation (reNEW NNF21CC0073729)资助。作者声明无利益冲突。注册号:无。
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引用次数: 0
Accurate identification of abnormal ploidy using an artificial intelligence model in preimplantation genetic testing. 利用人工智能模型在胚胎植入前基因检测中准确识别异常倍性。
IF 11.1 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-09-02 eCollection Date: 2025-01-01 DOI: 10.1093/hropen/hoaf054
Pingyuan Xie, Rijing Pang, Luyao Zeng, Shuoping Zhang, Lei Sun, Kaisen Yang, Xiaoyi Yang, Shuang Zhou, Senlin Zhang, Guangjian Liu, Yueqiu Tan, Liang Hu, Fei Gong, Jia Fei, Ge Lin
<p><strong>Study question: </strong>Can ultra-low-coverage whole-genome sequencing (ulc-WGS) accurately identify abnormal ploidy during preimplantation genetic testing (PGT)?</p><p><strong>Summary answer: </strong>The artificial intelligence (AI)-based PGT-Plus model demonstrates high accuracy in ploidy detection, offering a cost-effective solution that enhances clinical utility of PGT.</p><p><strong>What is known already: </strong>The predominant PGT for aneuploidy can identify chromosomal aneuploidies but cannot determine ploidy status. Transferring embryos with ploidy abnormalities can result in miscarriage and molar pregnancy. On the other hand, in ART, fertilization is assessed by morphological pronuclear assessment at the zygote stage. However, it has a low specificity in the prediction of abnormal ploidy status and embryos deemed abnormally fertilized can yield healthy pregnancies. Accurately identified abnormal ploidy in PGT-A can resolve current limitations and expand the utility range of PGT-A. Several studies have identified ploidy abnormalities; however, they were mainly based on single-nucleotide polymorphism (SNP) arrays or needed to combine additional targeted-next-generation sequencing (NGS) information. Studies based on ulc-WGS remain scarce.</p><p><strong>Study design size duration: </strong>The study consisted of two stages: methodology establishment and validation. An AI model, named PGT-Plus, was developed using 653 samples with known ploidy status, which was further validated using 792 different ploidy status samples. In the clinical application stage, the approach was used to analyse the ploidy status of 19 103 normally fertilized PGT blastocysts and 140 single pronucleus (1PN)-derived blastocysts collected between May 2022 and December 2023. All blastocysts were tested using trophectoderm biopsy and NGS.</p><p><strong>Participants/materials setting methods: </strong>The methodology is based on the ulc-WGS data. First, based on samples with known ploidy status: the heterozygosity rate of high-frequency biallelic SNPs, the likelihood ratio (LLR) of alleles was calculated under different assumptions ('both parental homologs' [BPH] from a single parent, 'single parental homolog' [SPH] from each parent, disomy, and monosomy) by leveraging allele frequencies and linkage disequilibrium (LD) measured in the 1000 genomes project database. Twenty-three continuous candidate features derived from heterozygosity rates and LLRs of chromosomes or selected windows were included to establish the ploidy prediction AI model. Gini importance analysis and multicollinearity mitigation was performed for feature selection, then the performance of Random Forest (RF), Support Vector Machine (SVM), and Logistic Regression for modelling was compared. Subsequently, the parameter optimization was performed based on the RF model. Ploidy constitution concordance was evaluated in known ploidy status samples. The frequency of abnormal ploidy in normal fert
研究问题:超低覆盖率全基因组测序(ulc-WGS)能否在胚胎植入前基因检测(PGT)中准确识别异常倍性?基于人工智能(AI)的PGT- plus模型在倍性检测方面具有很高的准确性,为提高PGT的临床应用提供了一种经济高效的解决方案。已知情况:非整倍体的主要PGT可以识别染色体非整倍体,但不能确定倍体状态。移植具有倍性异常的胚胎可导致流产和磨牙妊娠。另一方面,在抗逆转录病毒技术中,受精是通过合子阶段的形态原核评估来评估的。然而,它在预测异常倍性状态方面的特异性较低,被认为异常受精的胚胎可以产生健康的妊娠。准确识别PGT-A异常倍性可以解决目前PGT-A的局限性,扩大PGT-A的使用范围。一些研究已经发现了倍性异常;然而,它们主要基于单核苷酸多态性(SNP)阵列或需要结合额外的靶向下一代测序(NGS)信息。基于ulc-WGS的研究仍然很少。研究设计规模和持续时间:研究包括两个阶段:方法学建立和验证。利用已知倍性状态的653个样本建立了名为PGT-Plus的人工智能模型,并使用792个不同倍性状态的样本进一步验证了该模型。在临床应用阶段,该方法分析了2022年5月至2023年12月收集的19103个正常受精的PGT囊胚和140个单原核(1PN)来源囊胚的倍性状况。所有囊胚均采用滋养外胚层活检和NGS检测。参与者/材料设置方法:方法基于ulc-WGS数据。首先,基于已知倍性状态的样本:高频双等位基因snp的杂合率,利用1000基因组计划数据库中测量的等位基因频率和连锁不平衡(LD),在不同的假设(来自单亲的“双亲同源”[BPH],来自每个亲本的“单亲同源”[SPH],来自二体和单体)下计算等位基因的似然比(LLR)。纳入23个连续候选特征,这些特征来自于染色体的杂合率和llr或选择的窗口,以建立倍性预测AI模型。采用基尼重要性分析和多重共线性缓解方法进行特征选择,然后比较随机森林(RF)、支持向量机(SVM)和逻辑回归(Logistic Regression)的建模性能。随后,基于射频模型进行了参数优化。对已知倍性状态样本进行倍性结构一致性评价。评估正常受精PGT囊胚和1pn囊胚(包括常规IVF和ICSI)异常倍性的频率。主要结果和偶然性的作用:与SVM和Logistic回归相比,收集了11个特征用于模型架构;RF在倍性检测方面具有优异的性能。AI模型对全基因组单倍体(GW-UPD)的AUC为1,对三倍体的AUC为1,对二倍体的AUC为0.99。在792个验证样本中,99.5%的样本被人工智能模型成功检测,该模型对倍性分类的准确率为100%。在临床应用阶段,在19103份PGT样本中,19069份使用该模型成功分析,其中110份(0.57%)鉴定为异常倍性胚胎。其中,12.7%(14/110)为GW-UPD, 87.3%(96/110)为三倍体。移植二倍体囊胚5563例,成功妊娠3478例。随后对217例自然流产和935例产前诊断样本进行倍性分析,未发现异常倍性。此外,140个1PN胚胎中,40个(28.6%)表现为GW-UPD, 3个(2.1%)表现为三倍体,97个(69.3%)被确定为双亲本和正常受精。在97个双亲本胚胎中,46个为二倍体,11个为嵌合体,40个为非整倍体。在授精方式方面,ICSI中异常倍性的百分比明显高于常规IVF (P)。局限性:一些罕见的倍性异常,如具有相同数量染色体的多倍体和倍性嵌合体不能准确识别。此外,由于无法从父母双方获得DNA,因此无法确定异常倍性的起源。研究结果的更广泛意义:PGT-Plus AI模型提供了一种基于传统PGT-A数据的倍性评估方法,并直接集成到标准PGT-A工作流程中。
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引用次数: 0
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Human reproduction open
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