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Evaluating the diagnostic accuracy of androgen measurement in polycystic ovary syndrome: a systematic review and diagnostic meta-analysis to inform evidence-based guidelines 评估多囊卵巢综合征雄激素测量的诊断准确性:为循证指南提供信息的系统综述和诊断荟萃分析
IF 13.3 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-09-21 DOI: 10.1093/humupd/dmae028
Asmamaw Demis Bizuneh, Anju E Joham, Helena Teede, Aya Mousa, Arul Earnest, James M Hawley, Laura Smith, Ricardo Azziz, Wiebke Arlt, Chau Thien Tay
BACKGROUND Biochemical hyperandrogenism is a hallmark and diagnostic feature of polycystic ovary syndrome (PCOS). However, the most accurate androgen measurement for assessing biochemical hyperandrogenism in PCOS diagnosis remains uncertain. OBJECTIVE AND RATIONALE This systematic review aimed to assess different androgen measures [including total testosterone (TT), calculated free testosterone (cFT), free androgen index (FAI), androstenedione (A4), dehydroepiandrosterone sulfate (DHEAS), and dihydrotestosterone (DHT)] for accuracy in diagnosing biochemical hyperandrogenism in women with PCOS, to inform the 2023 International PCOS Evidence-based Guidelines. SEARCH METHODS To update evidence from the 2018 International PCOS Guidelines, a systematic search from 3 July 2017 to 23 June 2023 was conducted across Medline (Ovid), CINAHL, all EBM, EMBASE, and PsycInfo for articles evaluating androgens in the diagnosis of biochemical hyperandrogenism. The revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used to assess the risk of bias and applicability. A diagnostic test accuracy meta-analysis was performed using STATA 18 software. Summary sensitivity and specificity were calculated with 95% CIs using the bivariate model, while the hierarchical summary receiver operating characteristics (ROC) model was used to produce a summary ROC curve. OUTCOMES Of 23 studies reviewed, 18 were included in the meta-analysis, with data from 2857 participants (1650 with PCOS and 1207 controls). For diagnosing biochemical hyperandrogenism in PCOS, the pooled sensitivity, specificity, and AUC with 95% CI were for TT: 0.74 (0.63–0.82), 0.86 (0.77–0.91), and 0.87 (0.84–0.90); cFT: 0.89 (0.69–0.96), 0.83 (0.79–0.86), and 0.85 (0.81–0.88); FAI: 0.78 (0.70–0.83), 0.85 (0.76–0.90), and 0.87 (0.84–0.90); A4: 0.75 (0.60–0.86), 0.71 (0.51–0.85), and 0.80 (0.76–0.83); and DHEAS: 0.75 (0.61–0.85), 0.67 (0.48–0.81), and 0.77 (0.73–0.81), respectively. In subgroup analyses, liquid chromatography with tandem mass spectrometry (LC-MS/MS) had superior sensitivity for measuring cFT, FAI, A4, and DHEAS, and superior specificity for measuring TT, cFT, and FAI, compared to the direct immunoassay method. WIDER IMPLICATIONS Our results directly informed the 2023 International PCOS Guideline recommendations to use TT and FT as the first-line laboratory tests to assess biochemical hyperandrogenism in the diagnosis of PCOS. cFT should be assessed by equilibrium dialysis or ammonium sulfate precipitation, or calculated using FAI. If TT or cFT are not elevated, A4 and DHEAS could also be considered, noting their poorer specificity. Laboratories should utilize LC-MS/MS for androgen measurement given its high accuracy. Future studies should focus on establishing optimal normative cut-off values in large, unselected, and ethnically diverse cohorts of women. REGISTRATION NUMBER The review protocol was prepublished in the 2023 PCOS Guideline Technical Report (https://www.monash.edu/
背景生化高雄激素是多囊卵巢综合症(PCOS)的标志和诊断特征。然而,在多囊卵巢综合症诊断中,用于评估生化高雄激素症的最准确雄激素测量方法仍不确定。目的和依据 本系统综述旨在评估不同雄激素测量指标(包括总睾酮 (TT)、计算游离睾酮 (cFT)、游离雄激素指数 (FAI)、雄烯二酮 (A4)、硫酸脱氢表雄酮 (DHEAS) 和双氢睾酮 (DHT))在诊断多囊卵巢综合征女性生化高雄激素症方面的准确性,为 2023 年国际多囊卵巢综合征循证指南提供参考。检索方法 为了更新 2018 年《国际多囊卵巢综合征指南》中的证据,从 2017 年 7 月 3 日至 2023 年 6 月 23 日,在 Medline (Ovid)、CINAHL、所有 EBM、EMBASE 和 PsycInfo 中对评估诊断生化高雄激素症中雄激素的文章进行了系统检索。采用修订后的《诊断准确性研究质量评估》(QUADAS-2)来评估偏倚风险和适用性。使用 STATA 18 软件进行了诊断测试准确性荟萃分析。使用双变量模型计算出灵敏度和特异度的总和及 95% CIs,同时使用分层汇总接收器操作特征 (ROC) 模型生成汇总 ROC 曲线。结果 在所审查的 23 项研究中,有 18 项被纳入荟萃分析,数据来自 2857 名参与者(1650 名多囊卵巢综合症患者和 1207 名对照者)。对于诊断 PCOS 患者的生化高雄激素症,TT 的集合敏感性、特异性和 AUC(95% CI)分别为 0.74 (0.63-0.82)、0.86 (0.77-0.91) 和 0.87 (0.84-0.90);cFT 的集合敏感性、特异性和 AUC 分别为 0.89 (0.69-0.96)、0.83 (0.79-0.86) 和 0.85(0.81-0.88);FAI:0.78(0.70-0.83)、0.85(0.76-0.90)和 0.87(0.84-0.90);A4:0.75(0.60-0.86)、0.71(0.51-0.85)和 0.80(0.76-0.83);DHEAS:分别为 0.75(0.61-0.85)、0.67(0.48-0.81)和 0.77(0.73-0.81)。在分组分析中,与直接免疫测定法相比,液相色谱串联质谱法(LC-MS/MS)在测量 cFT、FAI、A4 和 DHEAS 方面具有更高的灵敏度,在测量 TT、cFT 和 FAI 方面具有更高的特异性。我们的研究结果为 2023 年国际多囊卵巢综合症指南提供了直接依据,该指南建议在诊断多囊卵巢综合症时将 TT 和 FT 作为评估生化高雄激素的一线实验室检测项目。如果 TT 或 cFT 没有升高,也可考虑检测 A4 和 DHEAS,但要注意它们的特异性较差。鉴于 LC-MS/MS 的高准确性,实验室应使用 LC-MS/MS 进行雄激素测量。未来的研究应侧重于在大型、非选择性和种族多样化的女性群体中建立最佳标准临界值。注册编号 评审方案已预先发布在《2023 年多囊卵巢综合症指南技术报告》中 (https://www.monash.edu/__data/assets/pdf_file/0010/3379591/TechnicalReport-2023.pdf)。
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引用次数: 0
Impact of Bisphenol A and its alternatives on oocyte health: a scoping review 双酚 A 及其替代品对卵母细胞健康的影响:范围审查
IF 13.3 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-09-15 DOI: 10.1093/humupd/dmae025
Alexandra E Peters, Emmalee A Ford, Shaun D Roman, Elizabeth G Bromfield, Brett Nixon, Kirsty G Pringle, Jessie M Sutherland
BACKGROUND Bisphenol A (BPA) is an endocrine disrupting chemical released from plastic materials, including food packaging and dental sealants, persisting in the environment and ubiquitously contaminating ecosystems and human populations. BPA can elicit an array of damaging health effects and, alarmingly, ‘BPA-free’ alternatives mirror these harmful effects. Bisphenol exposure can negatively impact female fertility, damaging both the ovary and oocytes therein. Such damage can diminish reproductive capacity, pregnancy success, and offspring health. Despite global government regulations in place to indicate ‘safe’ BPA exposure levels, these policies have not considered the effects of bisphenols on oocyte health. OBJECTIVE AND RATIONALE This scoping review was conducted to evaluate evidence on the effects of BPA and BPA alternatives on standardized parameters of oocyte health. In doing so, this review addresses a critical gap in the literature providing a comprehensive, up-to-date synthesis of the effects of bisphenols on oocyte health. SEARCH METHODS This scoping review was conducted in accordance with PRISMA guidelines. Four databases, Medline, Embase, Scopus, and Web of Science, were searched twice (23 February 2022 and 1 August 2023) to capture studies assessing mammalian oocyte health post-bisphenol exposure. Search terms regarding oocytes, ovarian follicles, and bisphenols were utilized to identify relevant studies. Manuscripts written in English and reporting the effect of any bisphenol on mammalian oocyte health from all years were included. Parameters for toxicological studies were evaluated, including the number of bisphenol concentrations/doses tested, dosing regimen, biological replicates and/or animal numbers, and statistical information (for human studies). Standardized parameters of oocyte health including follicle counts, oocyte yield, oocyte meiotic capacity, morphology of oocyte and cumulus cells, and oocyte meiotic spindle integrity were extracted across the studies. OUTCOMES After screening 3147 studies, 107 studies of either humans or mammalian animal models or humans were included. Of the in vitro exposure studies, 96.3% (26/27) and 94.1% (16/17) found at least one adverse effect on oocyte health using BPA or BPA alternatives (including BHPF, BPAF, BPB, BPF, and BPS), respectively. These included increased meiotic cell cycle arrest, altered morphology, and abnormal meiotic spindle/chromosomal alignment. In vivo, 85.7% (30/35) of studies on BPA and 92.3% (12/13) on BPA alternatives documented adverse effects on follicle development, morphology, or spindle/chromosome alignment. Importantly, these effects were recorded using levels below those deemed ‘safe’ for human exposure. Over half (11/21) of all human observational studies showed associations between higher urinary BPA levels and reduced antral follicle counts or oocyte yield in IVF patients. Recommendations are presented based on the identified shortcomings of the current e
背景 双酚 A(BPA)是一种干扰内分泌的化学物质,从食品包装和牙科密封剂等塑料材料中释放出来,长期存在于环境中,对生态系统和人类造成普遍污染。双酚 A 可对健康产生一系列有害影响,令人震惊的是,"不含双酚 A "的替代品也反映了这些有害影响。接触双酚会对女性的生育能力产生负面影响,损害卵巢和卵细胞。这种损害会降低生殖能力、怀孕成功率和后代健康。尽管全球政府都制定了相关法规来说明双酚 A 暴露的 "安全 "水平,但这些政策并未考虑双酚对卵母细胞健康的影响。目标和理由 本次范围界定审查旨在评估双酚 A 和双酚 A 替代品对卵母细胞健康标准参数影响的证据。在此过程中,本综述填补了文献中的一个重要空白,就双酚对卵母细胞健康的影响提供了全面、最新的综述。搜索方法 本次范围界定综述根据 PRISMA 指南进行。对 Medline、Embase、Scopus 和 Web of Science 四个数据库进行了两次检索(2022 年 2 月 23 日和 2023 年 8 月 1 日),以获取评估双酚暴露后哺乳动物卵母细胞健康状况的研究。利用有关卵母细胞、卵巢滤泡和双酚的检索词来确定相关研究。收录了用英语撰写的、报告任何双酚对哺乳动物卵母细胞健康影响的历年研究报告。对毒理学研究的参数进行了评估,包括测试的双酚浓度/剂量的数量、剂量方案、生物重复和/或动物数量以及统计信息(针对人类研究)。在所有研究中提取了卵母细胞健康的标准化参数,包括卵泡计数、卵母细胞产量、卵母细胞减数分裂能力、卵母细胞和积层细胞的形态以及卵母细胞减数分裂纺锤体的完整性。结果 筛选了 3147 项研究后,纳入了 107 项关于人类或哺乳动物模型或人类的研究。在体外暴露研究中,分别有 96.3% (26/27)和 94.1% (16/17)的研究发现,使用双酚 A 或双酚 A 替代品(包括双酚 A、双酚 AF、双酚 B、双酚 F 和双酚 S)至少会对卵母细胞健康产生一种不利影响。这些影响包括减数分裂细胞周期停滞、形态改变和减数分裂纺锤体/染色体排列异常。在体内,85.7%(30/35)关于双酚 A 的研究和 92.3%(12/13)关于双酚 A 替代品的研究记录了对卵泡发育、形态或纺锤体/染色体排列的不利影响。重要的是,这些影响都是在低于人体接触 "安全 "水平的情况下产生的。在所有人类观察性研究中,有一半以上(11/21)的研究表明,尿液中双酚 A 水平升高与体外受精患者前卵泡数或卵母细胞产量减少有关。根据已发现的现有证据的不足之处,并结合美国食品及药物管理局(FDA)对该领域未来研究的要求,提出了相关建议。更广泛的影响 这些数据强调了低水平双酚 A 和双酚 A 替代品暴露的有害影响,导致卵母细胞质量差和生育能力下降。这些结果对于推动国际社会修订与双酚 A 暴露相关的现行政策和指导方针具有重要价值。本研究为科学家提供了宝贵的资源,就研究设计、报告要素和终点测量提供了重要建议,以加强未来的研究。最终,本综述强调了卵母细胞健康是生殖毒理学研究中的一个基本重要终点,为今后研究干扰内分泌的化学品以改善生育结果指明了一个重要方向。
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引用次数: 0
Revealing the molecular landscape of human placenta: a systematic review and meta-analysis of single-cell RNA sequencing studies. 揭示人类胎盘的分子图谱:单细胞 RNA 测序研究的系统回顾和荟萃分析。
IF 14.8 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-07-01 DOI: 10.1093/humupd/dmae006
Emilie Derisoud, Hong Jiang, Allan Zhao, Pascale Chavatte-Palmer, Qiaolin Deng
<p><strong>Background: </strong>With increasing significance of developmental programming effects associated with placental dysfunction, more investigations are devoted to improving the characterization and understanding of placental signatures in health and disease. The placenta is a transitory but dynamic organ adapting to the shifting demands of fetal development and available resources of the maternal supply throughout pregnancy. Trophoblasts (cytotrophoblasts, syncytiotrophoblasts, and extravillous trophoblasts) are placental-specific cell types responsible for the main placental exchanges and adaptations. Transcriptomic studies with single-cell resolution have led to advances in understanding the placenta's role in health and disease. These studies, however, often show discrepancies in characterization of the different placental cell types.</p><p><strong>Objective and rationale: </strong>We aim to review the knowledge regarding placental structure and function gained from the use of single-cell RNA sequencing (scRNAseq), followed by comparing cell-type-specific genes, highlighting their similarities and differences. Moreover, we intend to identify consensus marker genes for the various trophoblast cell types across studies. Finally, we will discuss the contributions and potential applications of scRNAseq in studying pregnancy-related diseases.</p><p><strong>Search methods: </strong>We conducted a comprehensive systematic literature review to identify different cell types and their functions at the human maternal-fetal interface, focusing on all original scRNAseq studies on placentas published before March 2023 and published reviews (total of 28 studies identified) using PubMed search. Our approach involved curating cell types and subtypes that had previously been defined using scRNAseq and comparing the genes used as markers or identified as potential new markers. Next, we reanalyzed expression matrices from the six available scRNAseq raw datasets with cell annotations (four from first trimester and two at term), using Wilcoxon rank-sum tests to compare gene expression among studies and annotate trophoblast cell markers in both first trimester and term placentas. Furthermore, we integrated scRNAseq raw data available from 18 healthy first trimester and nine term placentas, and performed clustering and differential gene expression analysis. We further compared markers obtained with the analysis of annotated and raw datasets with the literature to obtain a common signature gene list for major placental cell types.</p><p><strong>Outcomes: </strong>Variations in the sampling site, gestational age, fetal sex, and subsequent sequencing and analysis methods were observed between the studies. Although their proportions varied, the three trophoblast types were consistently identified across all scRNAseq studies, unlike other non-trophoblast cell types. Notably, no marker genes were shared by all studies for any of the investigated cell types. Moreov
背景:随着与胎盘功能障碍相关的发育编程效应的重要性不断增加,越来越多的研究致力于改善健康和疾病中胎盘特征的描述和理解。胎盘是一个过渡性但动态的器官,在整个妊娠过程中适应胎儿发育和母体供应可用资源需求的变化。滋养细胞(细胞滋养细胞、合胞滋养细胞和体外滋养细胞)是胎盘特异性细胞类型,负责胎盘的主要交换和适应。具有单细胞分辨率的转录组研究使人们在了解胎盘在健康和疾病中的作用方面取得了进展。然而,这些研究往往显示不同胎盘细胞类型的特征存在差异:我们旨在回顾通过使用单细胞 RNA 测序(scRNAseq)获得的有关胎盘结构和功能的知识,然后比较细胞类型特异性基因,突出它们的异同点。此外,我们还打算找出不同研究中各种滋养层细胞类型的共识标记基因。最后,我们将讨论 scRNAseq 在妊娠相关疾病研究中的贡献和潜在应用:我们进行了全面的系统性文献综述,以确定人类母胎界面的不同细胞类型及其功能,重点是使用 PubMed 搜索 2023 年 3 月之前发表的所有原始胎盘 scRNAseq 研究和已发表的综述(共确定了 28 项研究)。我们的方法包括整理以前用 scRNAseq 定义的细胞类型和亚型,并比较用作标记或被鉴定为潜在新标记的基因。接下来,我们使用 Wilcoxon 秩和检验重新分析了六个可用的带有细胞注释的 scRNAseq 原始数据集(四个来自头胎,两个来自足月胎盘)中的表达矩阵,比较了不同研究中的基因表达,并注释了头胎和足月胎盘中的滋养层细胞标记。此外,我们还整合了来自 18 个健康初产胎盘和 9 个足月胎盘的 scRNAseq 原始数据,并进行了聚类和差异基因表达分析。我们还将通过分析注释数据集和原始数据集获得的标记与文献进行了比较,以获得主要胎盘细胞类型的通用特征基因列表:结果:不同研究的取样部位、孕龄、胎儿性别以及后续测序和分析方法均存在差异。尽管比例不同,但所有 scRNAseq 研究都一致鉴定出了三种滋养层细胞类型,这与其他非滋养层细胞类型不同。值得注意的是,在所有研究中,没有任何一种调查细胞类型的标记基因是相同的。此外,一项研究中新定义的大多数标记基因在其他研究中也没有发现。我们对滋养层细胞类型的分析也证实了这些差异,每项研究都发现了数百个潜在的标记基因,但各研究之间几乎没有重叠。我们分别从妊娠头三个月胎盘和足月胎盘中的 35 461 个和 23 378 个高质量细胞中获得了主要的胎盘细胞类型,包括以前在妊娠头三个月胎盘中未发现的血管周围细胞。重要的是,我们的荟萃分析在广泛整理的基础上提供了主要胎盘细胞类型的标记基因:本综述和荟萃分析强调了从 scRNAseq 数据中注释胎盘细胞类型达成共识的必要性。这里确定的标记基因可用于定义人类胎盘细胞类型,从而促进和提高滋养层细胞注释的可重复性。
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引用次数: 0
TGFβ signalling: a nexus between inflammation, placental health and preeclampsia throughout pregnancy. TGFβ 信号:整个孕期炎症、胎盘健康和子痫前期之间的联系。
IF 14.8 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-07-01 DOI: 10.1093/humupd/dmae007
Monika Horvat Mercnik, Carolin Schliefsteiner, Gonzalo Sanchez-Duffhues, Christian Wadsack
<p><strong>Background: </strong>The placenta is a unique and pivotal organ in reproduction, controlling crucial growth and cell differentiation processes that ensure a successful pregnancy. Placental development is a tightly regulated and dynamic process, in which the transforming growth factor beta (TGFβ) superfamily plays a central role. This family of pleiotropic growth factors is heavily involved in regulating various aspects of reproductive biology, particularly in trophoblast differentiation during the first trimester of pregnancy. TGFβ signalling precisely regulates trophoblast invasion and the cell transition from cytotrophoblasts to extravillous trophoblasts, which is an epithelial-to-mesenchymal transition-like process. Later in pregnancy, TGFβ signalling ensures proper vascularization and angiogenesis in placental endothelial cells. Beyond its role in trophoblasts and endothelial cells, TGFβ signalling contributes to the polarization and function of placental and decidual macrophages by promoting maternal tolerance of the semi-allogeneic foetus. Disturbances in early placental development have been associated with several pregnancy complications, including preeclampsia (PE) which is one of the severe complications. Emerging evidence suggests that TGFβ is involved in the pathogenesis of PE, thereby offering a potential target for intervention in the human placenta.</p><p><strong>Objective and rationale: </strong>This comprehensive review aims to explore and elucidate the roles of the major members of the TGFβ superfamily, including TGFβs, bone morphogenetic proteins (BMPs), activins, inhibins, nodals, and growth differentiation factors (GDFs), in the context of placental development and function. The review focusses on their interactions within the major cell types of the placenta, namely trophoblasts, endothelial cells, and immune cells, in both normal pregnancies and pregnancies complicated by PE throughout pregnancy.</p><p><strong>Search methods: </strong>A literature search was carried out using PubMed and Google Scholar, searching terms: 'TGF signalling preeclampsia', 'pregnancy TGF signalling', 'preeclampsia tgfβ', 'preeclampsia bmp', 'preeclampsia gdf', 'preeclampsia activin', 'endoglin preeclampsia', 'endoglin pregnancy', 'tgfβ signalling pregnancy', 'bmp signalling pregnancy', 'gdf signalling pregnancy', 'activin signalling pregnancy', 'Hofbauer cell tgfβ signalling', 'placental macrophages tgfβ', 'endothelial cells tgfβ', 'endothelium tgfβ signalling', 'trophoblast invasion tgfβ signalling', 'trophoblast invasion Smad', 'trophoblast invasion bmp', 'trophoblast invasion tgfβ', 'tgfβ preeclampsia', 'tgfβ placental development', 'TGFβ placental function', 'endothelial dysfunction preeclampsia tgfβ signalling', 'vascular remodelling placenta TGFβ', 'inflammation pregnancy tgfβ', 'immune response pregnancy tgfβ', 'immune tolerance pregnancy tgfβ', 'TGFβ pregnancy NK cells', 'bmp pregnancy NK cells', 'bmp pregnancy tregs', 'tgfβ pre
背景:胎盘是生殖过程中一个独特而关键的器官,控制着确保成功妊娠的关键生长和细胞分化过程。胎盘的发育是一个受到严格调控的动态过程,其中转化生长因子β(TGFβ)超家族发挥着核心作用。这个多效生长因子家族在很大程度上参与了生殖生物学各方面的调控,尤其是在妊娠头三个月的滋养细胞分化过程中。TGFβ 信号可精确调控滋养细胞的侵袭以及细胞从细胞滋养细胞向体外滋养细胞的转化,这是一个类似于上皮细胞向间质转化的过程。在妊娠后期,TGFβ 信号可确保胎盘内皮细胞的正常血管化和血管生成。除了在滋养层细胞和内皮细胞中的作用外,TGFβ 信号还通过促进母体对半异体胎儿的耐受性,促进胎盘和蜕膜巨噬细胞的极化和功能。胎盘早期发育紊乱与多种妊娠并发症有关,其中包括严重并发症之一的子痫前期(PE)。新的证据表明,TGFβ参与了子痫前期的发病机制,从而为干预人类胎盘提供了一个潜在的靶点。目的和依据:本综述旨在探讨和阐明TGFβ超家族主要成员在胎盘发育和功能中的作用,包括TGFβ、骨形态发生蛋白(BMP)、激活蛋白、抑制蛋白、节点因子和生长分化因子(GDF)。该综述重点关注它们在胎盘主要细胞类型(即滋养层细胞、内皮细胞和免疫细胞)中的相互作用,既包括正常妊娠,也包括整个妊娠过程中因 PE 而复杂化的妊娠:使用 PubMed 和 Google Scholar 进行文献检索,检索词为子痫前TGF信号"、"妊娠TGF信号"、"子痫前tgfβ信号"、"子痫前bmp信号"、"子痫前ggf信号"、"子痫前activin信号"、"子痫前endoglin信号"、"妊娠endoglin信号"、"妊娠tgfβ信号"、"妊娠bmp信号"、"妊娠ggf信号"、妊娠活化素信号"、"霍夫鲍尔细胞 tgfβ 信号"、"胎盘巨噬细胞 tgfβ"、"内皮细胞 tgfβ"、"内皮细胞 tgfβ 信号"、"滋养层细胞侵袭 tgfβ 信号"、"滋养层细胞侵袭 Smad"、"滋养层细胞侵袭 bmp"、滋养层母细胞侵袭 Tgfβ"、"子痫前期 Tgfβ"、"胎盘发育 Tgfβ"、"TGFβ 胎盘功能"、"子痫前期内皮功能障碍 Tgfβ 信号"、"血管重塑胎盘 TGFβ"、"妊娠炎症 Tgfβ"、免疫反应妊娠tgfβ"、"免疫耐受妊娠tgfβ"、"TGFβ妊娠NK细胞"、"bmp妊娠NK细胞"、"bmp妊娠Tregs"、"tgfβ妊娠Tregs"、"TGFβ胎盘NK细胞"、"TGFβ胎盘Tregs"、"子痫前期NK细胞"、"子痫前期Tregs"。仅采用 2023 年之前发表的英文文章:全面了解TGFβ信号及其在调节主要胎盘细胞类型相互关联的细胞功能方面的作用,有助于深入了解妊娠期间胎盘成功发育和胎儿生长所必需的过程。TGFβ 配体通过协调滋养层细胞的侵袭、血管化、免疫耐受和组织重塑,有助于健康的母胎界面正常运作。然而,TGFβ 信号的失调已被认为与 PE 的发病机制有关,在 PE 中观察到的滋养层细胞浅层侵入、血管重塑缺陷、子宫胎盘灌注减少、内皮细胞和免疫功能失调都受到 TGFβ 信号改变的影响:PE 中 TGFβ 信号的失调对研究和临床实践具有重要意义。需要进一步研究以了解其潜在机制,包括不同配体的作用及其在病理生理条件下的调节,从而发现新的治疗靶点。区分临床表现的 PE 亚型并全面研究不同胎盘细胞类型中的 TGFβ 信号是重要的第一步。要将这些知识付诸实践,需要临床前动物模型与新技术相结合。这也可能会改进人类研究模型并确定潜在的治疗目标,最终改善受影响妊娠的预后并减轻 PE 的负担。
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引用次数: 0
Navigating fertility dilemmas across the lifespan in girls with Turner syndrome-a scoping review. 特纳综合征女孩在整个生命周期中的生育困境--范围综述。
IF 14.8 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-07-01 DOI: 10.1093/humupd/dmae005
Sanne van der Coelen, Janielle van der Velden, Sapthami Nadesapillai, Didi Braat, Ronald Peek, Kathrin Fleischer
<p><strong>Background: </strong>Girls with Turner syndrome (TS) lack a partial or complete sex chromosome, which causes an accelerated decline of their ovarian reserve. Girls have to deal with several dilemmas related to their fertility, while only a limited number of them are referred to a fertility specialist and counselled about options of family planning on time.</p><p><strong>Objective and rationale: </strong>This scoping review provides an update of the literature on fertility in girls with TS throughout their lifespan and aims to propose a clinical practice guideline on fertility in TS.</p><p><strong>Search methods: </strong>Databases of PubMed, Embase, and Web of science were searched using the following key terms: Turner syndrome, fertility, puberty, pregnancy, sex-hormones, karyotype, fertility preservation, assisted reproductive techniques, and counselling, alongside relevant subject headings and synonymous terms. English language articles published since 2007 were critically reviewed. Pregnancies after using donated oocytes and data about girls with TS with Y-chromosomal content were excluded.</p><p><strong>Outcomes: </strong>This search identified 1269 studies of which 120 were extracted for the review. The prevalence of natural conception ranged from 15% to 48% in women with 45,X/46,XX, 1% to 3% in women with 45,X, and 4% to 9% in women with other TS karyotypes. When assessing a girl's fertility potential, it was crucial to determine the karyotype in two cell lines, because hidden mosaicism may exist. In addition to karyotype, assessment of anti-Müllerian hormone (AMH) played a significant role in estimating ovarian function. Girls with AMH above the detection limit were most likely to experience spontaneous thelarche, menarche, and ongoing ovarian function during the reproductive lifespan. Fertility preservation became more routine practice: vitrification of oocytes was reported in 58 girls with TS and a median of five oocytes were preserved per stimulation. Ovarian tissue cryopreservation has demonstrated the presence of follicles in approximately 30% of girls with TS, mostly in girls with mosaic-TS, spontaneous puberty, and AMH above the detection limit. Although girls and their parents appreciated receiving counselling on fertility in TS, only one in ten girls with TS received specialized counselling. Unfamiliarity with fertility preservation techniques or uncertainties regarding the eligibility of a girl for fertility preservation constituted barriers for healthcare professionals when discussing fertility with girls with TS.</p><p><strong>Wider implications: </strong>There currently is a high demand for fertility preservation techniques in girls with TS. A reliable prognostic model to determine which girls with TS might benefit from fertility preservation is lacking. Only a minority of these girls received comprehensive fertility counselling on the full spectrum of fertility, including uncertainties of fertility preservation, p
背景:特纳综合征(TS)女孩缺乏部分或完整的性染色体,这导致她们的卵巢储备功能加速衰退。女孩们不得不面对与生育有关的几种困境,而其中只有有限的女孩被转诊至生育专科,并得到及时的计划生育咨询。目的与依据:本范围综述提供了TS女孩一生中生育问题的最新文献,旨在提出TS女孩生育问题的临床实践指南:检索方法:使用以下关键术语在 PubMed、Embase 和 Web of science 等数据库中进行检索:特纳综合征、生育力、青春期、怀孕、性激素、核型、生育力保存、辅助生殖技术和咨询,以及相关主题词和同义词。对 2007 年以来发表的英文文章进行了严格审查。使用捐赠卵母细胞后怀孕的研究以及有关含有 Y 染色体的 TS 女孩的数据均被排除在外:此次检索共发现了 1269 项研究,其中 120 项被提取用于综述。45,X/46,XX女性的自然受孕率为15%至48%,45,X女性的自然受孕率为1%至3%,其他TS核型女性的自然受孕率为4%至9%。在评估女孩的生育能力时,确定两个细胞系的核型至关重要,因为可能存在隐性嵌合。除核型外,抗缪勒氏管激素(AMH)的评估在估计卵巢功能方面也发挥了重要作用。AMH 高于检测限的女孩最有可能出现自发性月经初潮、月经初潮,并在生育期内持续保持卵巢功能。生育力保存已成为一种常规做法:据报道,58 名 TS 女孩进行了卵母细胞玻璃化,每次刺激保存的卵母细胞中位数为 5 个。卵巢组织冷冻保存表明,约 30% 的 TS 女童体内存在卵泡,其中大部分是镶嵌型 TS、自发性青春期和 AMH 超过检测限的女童。尽管女孩及其父母对接受有关 TS 生育的咨询表示赞赏,但只有十分之一的 TS 女孩接受过专门的咨询。医护人员在与 TS 女孩讨论生育问题时,由于不熟悉生育力保存技术或不确定女孩是否有资格接受生育力保存,从而造成了障碍:目前,TS女孩对生育力保存技术的需求很大。目前还缺乏一个可靠的预后模型来确定哪些 TS 女孩可能会从保留生育力中受益。在这些女孩中,只有少数人接受过全面的生育咨询,包括生育力保存的不确定性、怀孕风险以及领养等替代方案。对于患有 TS 的女孩来说,保留生育力可能是一个可行的选择。但是,能否获得足够的卵细胞以实现活产的现实前景仍然是个问题。重要的是,女孩和家长应掌握必要的信息,以便在充分知情的情况下做出决定。
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引用次数: 0
Evolution of biotechnological advances and regenerative therapies for endometrial disorders: a systematic review 子宫内膜疾病的生物技术进步和再生疗法的发展:系统综述
IF 13.3 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-05-26 DOI: 10.1093/humupd/dmae013
Adolfo Rodríguez-Eguren, Clara Bueno-Fernandez, María Gómez-Álvarez, Emilio Francés-Herrero, Antonio Pellicer, José Bellver, Emre Seli, Irene Cervelló
BACKGROUND The establishment and maintenance of pregnancy depend on endometrial competence. Asherman syndrome (AS) and intrauterine adhesions (IUA), or endometrial atrophy (EA) and thin endometrium (TE), can either originate autonomously or arise as a result from conditions (i.e. endometritis or congenital hypoplasia), or medical interventions (e.g. surgeries, hormonal therapies, uterine curettage or radiotherapy). Affected patients may present an altered or inadequate endometrial lining that hinders embryo implantation and increases the risk of poor pregnancy outcomes and miscarriage. In humans, AS/IUA and EA/TE are mainly treated with surgeries or pharmacotherapy, however the reported efficacy of these therapeutic approaches remains unclear. Thus, novel regenerative techniques utilizing stem cells, growth factors, or tissue engineering have emerged to improve reproductive outcomes. OBJECTIVE AND RATIONALE This review comprehensively summarizes the methodologies and outcomes of emerging biotechnologies (cellular, acellular, and bioengineering approaches) to treat human endometrial pathologies. Regenerative therapies derived from human tissues or blood which were studied in preclinical models (in vitro and in vivo) and clinical trials are discussed. SEARCH METHODS A systematic search of full-text articles available in PubMed and Embase was conducted to identify original peer-reviewed studies published in English between January 2000 and September 2023. The search terms included: human, uterus, endometrium, Asherman syndrome, intrauterine adhesions, endometrial atrophy, thin endometrium, endometritis, congenital hypoplasia, curettage, radiotherapy, regenerative therapy, bioengineering, stem cells, vesicles, platelet-rich plasma, biomaterials, microfluidic, bioprinting, organoids, hydrogel, scaffold, sheet, miRNA, sildenafil, nitroglycerine, aspirin, growth hormone, progesterone, and estrogen. Preclinical and clinical studies on cellular, acellular, and bioengineering strategies to repair or regenerate the human endometrium were included. Additional studies were identified through manual searches. OUTCOMES From a total of 4366 records identified, 164 studies (3.8%) were included for systematic review. Due to heterogeneity in the study design and measured outcome parameters in both preclinical and clinical studies, the findings were evaluated qualitatively and quantitatively without meta-analysis. Groups using stem cell-based treatments for endometrial pathologies commonly employed mesenchymal stem cells (MSCs) derived from the human bone marrow or umbilical cord. Alternatively, acellular therapies based on platelet-rich plasma (PRP) or extracellular vesicles are gaining popularity. These are accompanied by the emergence of bioengineering strategies based on extracellular matrix (ECM)-derived hydrogels or synthetic biosimilars that sustain local delivery of cells and growth factors, reporting promising results. Combined therapies that target multipl
背景怀孕的建立和维持取决于子宫内膜的功能。阿瑟曼综合征(AS)和宫腔内粘连(IUA),或子宫内膜萎缩(EA)和子宫内膜薄(TE),既可能是自发性的,也可能是由于疾病(如子宫内膜炎或先天性发育不良)或医疗干预(如手术、激素疗法、子宫刮宫术或放疗)引起的。受影响的患者可能会出现子宫内膜改变或不足的情况,从而阻碍胚胎着床,增加不良妊娠结局和流产的风险。在人类中,AS/IUA 和 EA/TE 主要通过手术或药物治疗进行治疗,但这些治疗方法的疗效仍不明确。因此,利用干细胞、生长因子或组织工程的新型再生技术应运而生,以改善生殖结果。目标和理由 本综述全面总结了治疗人类子宫内膜病变的新兴生物技术(细胞、细胞和生物工程方法)的方法和结果。文中讨论了在临床前模型(体外和体内)和临床试验中研究的源自人体组织或血液的再生疗法。检索方法 对PubMed和Embase中的全文文章进行了系统检索,以确定2000年1月至2023年9月期间以英文发表的、经同行评审的原创研究。搜索关键词包括人类、子宫、子宫内膜、阿什曼综合征、宫腔内粘连、子宫内膜萎缩、子宫内膜薄、子宫内膜炎、先天性子宫发育不良、刮宫、放射治疗、再生治疗、生物工程、干细胞、囊泡、富血小板血浆、生物材料、微流体、生物打印、类器官、水凝胶、支架、薄片、miRNA、西地那非、硝酸甘油、阿司匹林、生长激素、孕酮和雌激素。有关修复或再生人类子宫内膜的细胞、细胞和生物工程策略的临床前和临床研究也包括在内。其他研究则通过人工搜索确定。结果 从总共 4366 条记录中,有 164 项研究(3.8%)被纳入系统综述。由于临床前和临床研究在研究设计和测量结果参数方面存在异质性,因此在未进行荟萃分析的情况下,对研究结果进行了定性和定量评估。以干细胞为基础治疗子宫内膜病变的研究小组通常采用从骨髓或脐带中提取的间充质干细胞(MSCs)。另外,基于富血小板血浆(PRP)或细胞外囊泡的细胞疗法也越来越受欢迎。与此同时,基于细胞外基质(ECM)衍生的水凝胶或合成生物仿制药的生物工程策略也在不断涌现,可维持细胞和生长因子的局部输送,并取得了可喜的成果。针对组织修复和再生多个方面的综合疗法仍处于临床前试验阶段,但已显示出转化价值。本综述重点介绍了已测试过的各种治疗材料来源、给药方法和载体。更广泛的意义 促进子宫内膜增殖、血管发育和组织修复的疗法可能有助于恢复子宫内膜功能,并最终恢复生育能力。基于现有的证据、成本、可及性和疗法的可用性,我们建议开发三重打击再生策略,可能将高产间充质干细胞(如来自骨髓或脐带的间充质干细胞)与细胞治疗(PRP)相结合,也可能与 ECM 水凝胶相结合。生物技术的进步与临床前模型的研究成果将为开发针对导致不孕的子宫内膜疾病(如 AS/IUA、EA/TE 和子宫内膜炎)患者的个性化治疗方案铺平道路。注册号 https://osf.io/th8yf/
{"title":"Evolution of biotechnological advances and regenerative therapies for endometrial disorders: a systematic review","authors":"Adolfo Rodríguez-Eguren, Clara Bueno-Fernandez, María Gómez-Álvarez, Emilio Francés-Herrero, Antonio Pellicer, José Bellver, Emre Seli, Irene Cervelló","doi":"10.1093/humupd/dmae013","DOIUrl":"https://doi.org/10.1093/humupd/dmae013","url":null,"abstract":"BACKGROUND The establishment and maintenance of pregnancy depend on endometrial competence. Asherman syndrome (AS) and intrauterine adhesions (IUA), or endometrial atrophy (EA) and thin endometrium (TE), can either originate autonomously or arise as a result from conditions (i.e. endometritis or congenital hypoplasia), or medical interventions (e.g. surgeries, hormonal therapies, uterine curettage or radiotherapy). Affected patients may present an altered or inadequate endometrial lining that hinders embryo implantation and increases the risk of poor pregnancy outcomes and miscarriage. In humans, AS/IUA and EA/TE are mainly treated with surgeries or pharmacotherapy, however the reported efficacy of these therapeutic approaches remains unclear. Thus, novel regenerative techniques utilizing stem cells, growth factors, or tissue engineering have emerged to improve reproductive outcomes. OBJECTIVE AND RATIONALE This review comprehensively summarizes the methodologies and outcomes of emerging biotechnologies (cellular, acellular, and bioengineering approaches) to treat human endometrial pathologies. Regenerative therapies derived from human tissues or blood which were studied in preclinical models (in vitro and in vivo) and clinical trials are discussed. SEARCH METHODS A systematic search of full-text articles available in PubMed and Embase was conducted to identify original peer-reviewed studies published in English between January 2000 and September 2023. The search terms included: human, uterus, endometrium, Asherman syndrome, intrauterine adhesions, endometrial atrophy, thin endometrium, endometritis, congenital hypoplasia, curettage, radiotherapy, regenerative therapy, bioengineering, stem cells, vesicles, platelet-rich plasma, biomaterials, microfluidic, bioprinting, organoids, hydrogel, scaffold, sheet, miRNA, sildenafil, nitroglycerine, aspirin, growth hormone, progesterone, and estrogen. Preclinical and clinical studies on cellular, acellular, and bioengineering strategies to repair or regenerate the human endometrium were included. Additional studies were identified through manual searches. OUTCOMES From a total of 4366 records identified, 164 studies (3.8%) were included for systematic review. Due to heterogeneity in the study design and measured outcome parameters in both preclinical and clinical studies, the findings were evaluated qualitatively and quantitatively without meta-analysis. Groups using stem cell-based treatments for endometrial pathologies commonly employed mesenchymal stem cells (MSCs) derived from the human bone marrow or umbilical cord. Alternatively, acellular therapies based on platelet-rich plasma (PRP) or extracellular vesicles are gaining popularity. These are accompanied by the emergence of bioengineering strategies based on extracellular matrix (ECM)-derived hydrogels or synthetic biosimilars that sustain local delivery of cells and growth factors, reporting promising results. Combined therapies that target multipl","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"31 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141098016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A comprehensive review of the new FIGO classification of ovulatory disorders. 全面回顾 FIGO 对排卵障碍的新分类。
IF 14.8 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-05-02 DOI: 10.1093/humupd/dmae003
Adam H Balen, Jennifer Tamblyn, Karolina Skorupskaite, Malcolm G Munro

Background: The World Health Organization (WHO) system for the classification of disorders of ovulation was produced 50 years ago and, by international consensus, has been updated by the International Federation of Gynecology and Obstetrics (FIGO).

Objective and rationale: This review outlines in detail each component of the FIGO HyPO-P (hypothalamic, pituitary, ovarian, PCOS) classification with a concise description of each cause, and thereby provides a systematic method for diagnosis and management.

Search methods: We searched the published articles in the PubMed database in the English-language literature until October 2022, containing the keywords ovulatory disorders; ovulatory dysfunction; anovulation, and each subheading in the FIGO HyPO-P classification. We did not include abstracts or conference proceedings because the data are usually difficult to assess.

Outcomes: We present the most comprehensive review of all disorders of ovulation, published systematically according to the logical FIGO classification.

Wider implications: Improving the diagnosis of an individual's ovulatory dysfunction will significantly impact clinical practice by enabling healthcare practitioners to make a precise diagnosis and plan appropriate management.

背景:目的和依据:本综述详细概述了FIGO HyPO-P(下丘脑、垂体、卵巢、多囊卵巢综合征)分类的每个组成部分,并对每个病因进行了简明扼要的描述,从而为诊断和管理提供了系统的方法:我们检索了PubMed数据库中截至2022年10月发表的英文文献,其中包含排卵障碍、排卵功能障碍、无排卵等关键词以及FIGO HyPO-P分类中的每个子标题。我们没有收录摘要或会议论文集,因为这些数据通常难以评估:结果:我们对所有排卵障碍进行了最全面的综述,并根据合理的 FIGO 分类进行了系统的出版:更广泛的意义:改进对个人排卵功能障碍的诊断将对临床实践产生重大影响,使医疗从业人员能够做出精确诊断并制定适当的治疗计划。
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引用次数: 0
Sexual function in women with polycystic ovary syndrome: a systematic review and meta-analysis. 多囊卵巢综合征妇女的性功能:系统回顾和荟萃分析。
IF 14.8 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-05-02 DOI: 10.1093/humupd/dmad034
Hester Pastoor, Aya Mousa, Hanneke Bolt, Wichor Bramer, Tania S Burgert, Anuja Dokras, Chau Thien Tay, Helena J Teede, Joop Laven

Background: Polycystic ovary syndrome (PCOS) is a common and distressing endocrine disorder associated with lower quality of life, subfertility, diabetes, cardiovascular disease, depression, anxiety, and eating disorders. PCOS characteristics, its comorbidities, and its treatment can potentially influence sexual function. However, studies on sexual function in women with PCOS are limited and contradictory.

Objective and rationale: The aim was to perform a systematic review of the published literature on sexual function in women with PCOS and assess the quality of the research and certainty of outcomes, to inform the 2023 International Guidelines for the Assessment and Management of PCOS.

Search methods: Eight electronic databases were searched until 1 June 2023. Studies reporting on sexual function using validated sexuality questionnaires or visual analogue scales (VAS) in PCOS populations were included. Random-effects models were used for meta-analysis comparing PCOS and non-PCOS groups with Hedges' g as the standardized mean difference. Study quality and certainty of outcomes were assessed by risk of bias assessments and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method according to Cochrane. Funnel plots were visually inspected for publication bias.

Outcomes: There were 32 articles included, of which 28 used validated questionnaires and four used VAS. Pooled Female Sexual Function Index (FSFI) scores in random-effects models showed worse sexual function across most subdomains in women with PCOS, including arousal (Hedges's g [Hg] [95% CI] = -0.35 [-0.53, -0.17], I2 = 82%, P < 0.001), lubrication (Hg [95% CI] = -0.54 [-0.79, -0.30], I2 = 90%, P < 0.001), orgasm (Hg [95% CI] = -0.37 [-0.56, -0.19], I2 = 83%, P < 0.001), and pain (Hg [95% CI] = -0.36 [-0.59, -0.13] I2 = 90%, P < 0.001), as well as total sexual function (Hg [95% CI] = -0.75 [-1.37, -0.12], I2 = 98%, P  =  0.02) and sexual satisfaction (Hg [95% CI] = -0.31 [-0.45, -0.18], I2 = 68%, P < 0.001). Sensitivity and subgroup analyses based on fertility status and body mass index (BMI) did not alter the direction or significance of the results. Meta-analysis on the VAS studies demonstrated the negative impact of excess body hair on sexuality, lower sexual attractiveness, and lower sexual satisfaction in women with PCOS compared to controls, with no differences in the perceived importance of a satisfying sex life. No studies assessed sexual distress. GRADE assessments showed low certainty across all outcomes.

Wider implications: Psychosexual function appears to be impaired in those with PCOS, but there is a lack of evidence on the related distress scores, which are required to meet the criteria for psychosexual dysfunction. Health care professionals should discuss sexual function and distress and be aware of the multifactorial influences on sex

背景:多囊卵巢综合征(PCOS)是一种常见且令人苦恼的内分泌疾病,与生活质量下降、不孕、糖尿病、心血管疾病、抑郁、焦虑和饮食失调有关。多囊卵巢综合症的特征、并发症和治疗方法都有可能影响性功能。目的和依据:该研究旨在对已发表的有关多囊卵巢综合征女性性功能的文献进行系统性回顾,评估研究质量和结果的确定性,为《2023 年多囊卵巢综合征评估和管理国际指南》提供参考:检索方法:在 2023 年 6 月 1 日前检索了八个电子数据库。纳入了使用有效的性行为问卷或视觉模拟量表(VAS)对多囊卵巢综合征人群的性功能进行报告的研究。采用随机效应模型对多囊卵巢综合症组和非多囊卵巢综合症组进行荟萃分析,以 Hedges'g 作为标准化平均差。根据 Cochrane 的偏倚风险评估和推荐、评估、发展和评价分级法(GRADE)评估研究质量和结果的确定性。对漏斗图进行目视检查,以确定是否存在发表偏倚:共纳入 32 篇文章,其中 28 篇使用有效问卷,4 篇使用 VAS。在随机效应模型中汇总的女性性功能指数(FSFI)得分显示,患有多囊卵巢综合征的女性在大多数子领域的性功能都较差,包括唤起(Hedges's g [Hg] [95% CI] = -0.35 [-0.53, -0.17],I2 = 82%,P 更广泛的意义:多囊卵巢综合症患者的性心理功能似乎受到了损害,但相关的痛苦评分缺乏证据,而痛苦评分是达到性心理功能障碍标准的必要条件。医护人员应讨论性功能和困扰,并了解多囊卵巢综合征患者性功能的多因素影响。未来的研究需要同时评估性心理功能和困扰,以帮助了解多囊卵巢综合症患者性心理功能障碍的程度。最后,在未来的研究中应纳入更多不同的人群(如非异性恋和更多不同种族的群体),还应评估治疗性功能障碍的疗效(如生活方式和药物干预)。
{"title":"Sexual function in women with polycystic ovary syndrome: a systematic review and meta-analysis.","authors":"Hester Pastoor, Aya Mousa, Hanneke Bolt, Wichor Bramer, Tania S Burgert, Anuja Dokras, Chau Thien Tay, Helena J Teede, Joop Laven","doi":"10.1093/humupd/dmad034","DOIUrl":"10.1093/humupd/dmad034","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is a common and distressing endocrine disorder associated with lower quality of life, subfertility, diabetes, cardiovascular disease, depression, anxiety, and eating disorders. PCOS characteristics, its comorbidities, and its treatment can potentially influence sexual function. However, studies on sexual function in women with PCOS are limited and contradictory.</p><p><strong>Objective and rationale: </strong>The aim was to perform a systematic review of the published literature on sexual function in women with PCOS and assess the quality of the research and certainty of outcomes, to inform the 2023 International Guidelines for the Assessment and Management of PCOS.</p><p><strong>Search methods: </strong>Eight electronic databases were searched until 1 June 2023. Studies reporting on sexual function using validated sexuality questionnaires or visual analogue scales (VAS) in PCOS populations were included. Random-effects models were used for meta-analysis comparing PCOS and non-PCOS groups with Hedges' g as the standardized mean difference. Study quality and certainty of outcomes were assessed by risk of bias assessments and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method according to Cochrane. Funnel plots were visually inspected for publication bias.</p><p><strong>Outcomes: </strong>There were 32 articles included, of which 28 used validated questionnaires and four used VAS. Pooled Female Sexual Function Index (FSFI) scores in random-effects models showed worse sexual function across most subdomains in women with PCOS, including arousal (Hedges's g [Hg] [95% CI] = -0.35 [-0.53, -0.17], I2 = 82%, P < 0.001), lubrication (Hg [95% CI] = -0.54 [-0.79, -0.30], I2 = 90%, P < 0.001), orgasm (Hg [95% CI] = -0.37 [-0.56, -0.19], I2 = 83%, P < 0.001), and pain (Hg [95% CI] = -0.36 [-0.59, -0.13] I2 = 90%, P < 0.001), as well as total sexual function (Hg [95% CI] = -0.75 [-1.37, -0.12], I2 = 98%, P  =  0.02) and sexual satisfaction (Hg [95% CI] = -0.31 [-0.45, -0.18], I2 = 68%, P < 0.001). Sensitivity and subgroup analyses based on fertility status and body mass index (BMI) did not alter the direction or significance of the results. Meta-analysis on the VAS studies demonstrated the negative impact of excess body hair on sexuality, lower sexual attractiveness, and lower sexual satisfaction in women with PCOS compared to controls, with no differences in the perceived importance of a satisfying sex life. No studies assessed sexual distress. GRADE assessments showed low certainty across all outcomes.</p><p><strong>Wider implications: </strong>Psychosexual function appears to be impaired in those with PCOS, but there is a lack of evidence on the related distress scores, which are required to meet the criteria for psychosexual dysfunction. Health care professionals should discuss sexual function and distress and be aware of the multifactorial influences on sex","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"323-340"},"PeriodicalIF":14.8,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11063549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139492866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Driving factors in treatment decision-making of patients seeking medical assistance for infertility: a systematic review. 不孕症患者寻求医疗救助时做出治疗决策的驱动因素:系统综述。
IF 14.8 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-05-02 DOI: 10.1093/humupd/dmae001
Felicia von Estorff, Monique H Mochtar, Vicky Lehmann, Madelon van Wely
<p><strong>Background: </strong>ART differs in effectiveness, side-effects, administration, and costs. To improve the decision-making process, we need to understand what factors patients consider to be most important.</p><p><strong>Objective and rationale: </strong>We conducted this systematic review to assess which aspects of ART treatment (effectiveness, safety, burden, costs, patient-centeredness, and genetic parenthood) are most important in the decision-making of patients with an unfulfilled wish to have a child.</p><p><strong>Search methods: </strong>We searched studies indexed in Embase, PubMed, PsycINFO, and CINAHL prior to November 2023. Discrete choice experiments (DCEs), surveys, interviews, and conjoint analyses (CAs) about ART were included. Studies were included if they described two or more of the following attributes: effectiveness, safety, burden, costs, patient-centeredness, and genetic parenthood.Participants were men and women with an unfulfilled wish to have a child. From each DCE/CA study, we extracted the beta-coefficients and calculated the relative importance of treatment attributes or, in case of survey studies, extracted results. We assessed the risk of bias using the rating developed by the Grading of Recommendations Assessment, Development and Evaluation working group. Attributes were classified into effectiveness, safety, burden, costs, patient-centeredness, genetic parenthood, and others.</p><p><strong>Outcomes: </strong>The search identified 938 studies of which 20 were included: 13 DCEs, three survey studies, three interview studies, and one conjoint analysis, with a total of 12 452 patients. Per study, 47-100% of the participants were women. Studies were assessed as having moderate to high risk of bias (critical: six studies, serious: four studies, moderate: nine studies, low: one study). The main limitation was the heterogeneity in the questionnaires and methodology utilized. Studies varied in the number and types of assessed attributes. Patients' treatment decision-making was mostly driven by effectiveness, followed by safety, burden, costs, and patient-centeredness. Effectiveness was rated as the first or second most important factor in 10 of the 12 DCE studies (83%) and the relative importance of effectiveness varied between 17% and 63%, with a median of 34% (moderate certainty of evidence). Of eight studies evaluating safety, five studies valued safety as the first or second most important factor (63%), and the relative importance ranged from 8% to 35% (median 23%) (moderate certainty of evidence). Cost was rated as first or second most important in five of 10 studies, and the importance relative to the other attributes varied between 5% and 47% (median 23%) (moderate certainty of evidence). Burden was rated as first or second by three of 10 studies (30%) and the relative importance varied between 1% and 43% (median 13%) (low certainty of evidence). Patient-centeredness was second most important in one of fi
背景:抗逆转录病毒疗法在效果、副作用、管理和成本方面各不相同。为了改善决策过程,我们需要了解患者认为哪些因素最重要:我们进行了这项系统性综述,以评估 ART 治疗的哪些方面(有效性、安全性、负担、成本、以患者为中心和遗传亲子关系)对未实现生育愿望的患者的决策最为重要:我们检索了 2023 年 11 月之前在 Embase、PubMed、PsycINFO 和 CINAHL 中收录的研究。其中包括关于抗逆转录病毒疗法的离散选择实验(DCE)、调查、访谈和联合分析(CA)。如果研究描述了以下两个或两个以上的属性:有效性、安全性、负担、成本、以患者为中心和遗传亲子关系,则被纳入研究。我们从每项 DCE/CA 研究中提取了 beta 系数,并计算了治疗属性的相对重要性,如果是调查研究,则提取了结果。我们使用 "建议评估、开发和评价分级 "工作组制定的分级标准对偏倚风险进行了评估。属性分为有效性、安全性、负担、成本、以患者为中心、遗传亲子关系及其他:搜索共发现 938 项研究,其中 20 项被纳入:13 项 DCE、3 项调查研究、3 项访谈研究和 1 项联合分析,共涉及 12 452 名患者。每项研究中,47%-100% 的参与者为女性。研究被评估为存在中度至高度偏倚风险(严重:6 项研究;严重:4 项研究;中度:9 项研究;低度:1 项研究)。主要的局限性在于所使用的问卷和方法存在异质性。研究在评估属性的数量和类型方面存在差异。患者的治疗决策主要受有效性驱动,其次是安全性、负担、成本和以患者为中心。在 12 项 DCE 研究中,有 10 项(83%)将疗效评为第一或第二重要因素,疗效的相对重要性介于 17% 与 63% 之间,中位数为 34%(中度证据确定性)。在 8 项评估安全性的研究中,5 项研究将安全性列为第一或第二重要因素(63%),相对重要性介于 8% 与 35% 之间(中位数为 23%)(中度证据确定性)。在 10 项研究中,有 5 项将成本评为第一或第二重要因素,相对于其他属性的重要性介于 5% 与 47% 之间(中位数为 23%)(中等证据确定性)。在 10 项研究中,有 3 项(30%)将负担评为第一或第二重要,其相对重要性介于 1% 与 43% 之间(中位数为 13%)(证据确定性较低)。五项研究中有一项(20%)将 "以病人为中心 "评为第二重要,其相对重要性介于 7% 与 24% 之间(中位数为 14%)(证据确定性低)。研究结果表明,患者愿意用一些有效性来换取更多的安全性,或减轻负担和以患者为中心。在对安全性进行评估时,患儿的安全被认为比母亲的安全更重要。如果能获得有效性、安全性或更低的成本,患者更有可能接受更大的负担(周期取消、注射次数、医院就诊次数、时间)。在以病人为中心方面,提供信息和医生态度被认为是最重要的,其次是参与决策和由同一医疗专业人员继续治疗。非遗传亲子关系对决策的影响并不明显:本综述的研究结果可用于未来的偏好研究,并可帮助医疗专业人员指导患者做出决策,从而实现更加以患者为中心的方法。
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引用次数: 0
Assessing the influence of preconception diet on male fertility: a systematic scoping review. 评估孕前饮食对男性生育能力的影响:系统性范围研究。
IF 14.8 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-05-02 DOI: 10.1093/humupd/dmad035
Cathryn A Tully, Simon Alesi, Nicole O McPherson, David J Sharkey, Xiao Tong Teong, Chau Thien Tay, Thais Rasia Silva, Carolyn Puglisi, Jacqueline P Barsby, Lisa J Moran, Jessica A Grieger, Aya Mousa
<p><strong>Background: </strong>The last decade has seen increased research on the relationship between diet and male fertility, but there are no clearly defined nutritional recommendations for men in the preconception period to support clinical fertility outcomes.</p><p><strong>Objective and rationale: </strong>The purpose of this scoping review is to examine the extent and range of research undertaken to evaluate the effect(s) of diet in the preconception period on male clinical fertility and reproductive outcomes.</p><p><strong>Search methods: </strong>Four electronic databases (MEDLINE and EMBASE via Ovid, CAB Direct, and CINAHL via EBSCO) were searched from inception to July 2023 for randomized controlled trials (RCTs) and observational studies (prospective/retrospective, case-control, and cross-sectional). Intervention studies in male participants or couples aiming to achieve dietary or nutritional change, or non-intervention studies examining dietary or nutritional components (whole diets, dietary patterns, food groups or individual foods) in the preconception period were included. Controls were defined as any comparison group for RCTs, and any/no comparison for observational studies. Primary outcomes of interest included the effect(s) of male preconception diet on clinical outcomes such as conception (natural or via ART), pregnancy rates and live birth rates. Secondary outcomes included time to conception and sperm parameters.</p><p><strong>Outcomes: </strong>A total of 37 studies were eligible, including one RCT and 36 observational studies (prospective, cross-sectional, and case-control studies; four studies in non-ART populations) published between 2008 and 2023. Eight reported clinical outcomes, 26 reported on secondary outcomes, and three reported on both. The RCT did not assess clinical outcomes but found that tomato juice may benefit sperm motility. In observational studies, some evidence suggested that increasing fish or reducing sugar-sweetened beverages, processed meat or total fat may improve fecundability. Evidence for other clinical outcomes, such as pregnancy rates or live birth rates, showed no relationship with cereals, soy and dairy, and inconsistent relationships with consuming red meat or a 'healthy diet' pattern. For improved sperm parameters, limited evidence supported increasing fish, fats/fatty acids, carbohydrates and dairy, and reducing processed meat, while the evidence for fruits, vegetables, cereals, legumes, eggs, red meat and protein was inconsistent. Healthy diet patterns in general were shown to improve sperm health.</p><p><strong>Wider implications: </strong>Specific dietary recommendations for improving male fertility are precluded by the lack of reporting on clinical pregnancy outcomes, heterogeneity of the available literature and the paucity of RCTs to determine causation or to rule out reverse causation. There may be some benefit from increasing fish, adopting a healthy dietary pattern, and reducing c
背景:过去十年中,有关饮食与男性生育力之间关系的研究不断增加,但目前尚无明确的孕前男性营养建议来支持临床生育力结果。目的与依据:本范围综述旨在研究孕前饮食对男性临床生育力和生殖结果影响的程度和范围:检索了四个电子数据库(通过 Ovid 检索的 MEDLINE 和 EMBASE、通过 EBSCO 检索的 CAB Direct 和 CINAHL)中从开始到 2023 年 7 月的随机对照试验 (RCT) 和观察性研究(前瞻性/回顾性、病例对照和横断面)。包括以男性参与者或夫妇为对象、旨在实现饮食或营养改变的干预研究,或检查孕前饮食或营养成分(整体饮食、饮食模式、食物组或个别食物)的非干预研究。研究性试验的对照组定义为任何对比组,观察性研究的对照组定义为任何对比组/无对比组。主要研究结果包括男性孕前饮食对受孕(自然受孕或通过抗逆转录病毒疗法受孕)、怀孕率和活产率等临床结果的影响。次要结果包括受孕时间和精子参数:共有 37 项研究符合条件,其中包括一项 RCT 和 36 项观察性研究(前瞻性、横断面和病例对照研究;四项研究针对非 ART 群体),这些研究发表于 2008 年至 2023 年之间。其中 8 项报告了临床结果,26 项报告了次要结果,3 项报告了两者。研究性试验没有评估临床结果,但发现番茄汁可能有益于精子活力。在观察性研究中,一些证据表明,增加鱼类或减少含糖饮料、加工肉类或总脂肪可提高受精能力。关于其他临床结果(如怀孕率或活产率)的证据显示,与谷物、大豆和奶制品没有关系,与食用红肉或 "健康饮食 "模式的关系也不一致。在改善精子参数方面,有限的证据支持增加鱼类、脂肪/脂肪酸、碳水化合物和乳制品,减少加工肉类,而水果、蔬菜、谷物、豆类、鸡蛋、红肉和蛋白质的证据不一致。一般健康的饮食模式可改善精子健康:由于缺乏有关临床妊娠结果的报告、现有文献的异质性以及用于确定因果关系或排除反向因果关系的研究性临床试验极少,因此无法提出改善男性生育能力的具体饮食建议。增加鱼类摄入量、采用健康的膳食模式、减少含糖饮料和加工肉类的摄入量可能会带来一些益处,但目前还不清楚这些益处是否超出了精子参数的范围,从而改善了临床生育能力。我们鼓励开展更多的研究,探讨男性生育力方面的整体饮食而非单一食物或营养成分,尤其是在可行的情况下通过研究性对照试验(RCTs)进行研究。有必要对核心生育力结果进行进一步评估,这需要在高质量的前瞻性研究和研究性临床试验中进行仔细规划。这些研究可以为制定有针对性的膳食指南奠定基础,并提高男性在孕前成功生育的前景。对孕前饮食的系统性研究表明,增加鱼类,减少含糖饮料、加工肉类和总脂肪可提高男性生育能力,而摄入健康饮食、鱼类、脂肪/脂肪酸、碳水化合物和乳制品,减少加工肉类可改善精子健康。
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Human Reproduction Update
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