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Transcriptomic integrity of human oocytes used in ARTs: technical and intrinsic factor effects. 用于 ART 的人类卵母细胞转录组的完整性：技术和内在因素的影响。
IF 14.8 1区 医学 Q1 OBSTETRICS & GYNECOLOGY
Human Reproduction Update
Pub Date : 2024-01-03 DOI: 10.1093/humupd/dmad025
Bastien Ducreux, Catherine Patrat, Jacquetta Trasler, Patricia Fauque
<p><strong>Background: </strong>Millions of children have been born throughout the world thanks to ARTs, the harmlessness of which has not yet been fully demonstrated. For years, efforts to evaluate the specific effects of ART have focused on the embryo; however, it is the oocyte quality that mainly dictates first and foremost the developmental potential of the future embryo. Ovarian stimulation, cryopreservation, and IVM are sometimes necessary steps to obtain a mature oocyte, but they could alter the appropriate expression of the oocyte genome. Additionally, it is likely that female infertility, environmental factors, and lifestyle have a significant influence on oocyte transcriptomic quality, which may interfere with the outcome of an ART attempt.</p><p><strong>Objective and rationale: </strong>The objective of this review is to identify transcriptomic changes in the human oocyte caused by interventions specific to ART but also intrinsic factors such as age, reproductive health issues, and lifestyle. We also provide recommendations for future good practices to be conducted when attempting ART.</p><p><strong>Search methods: </strong>An in-depth literature search was performed on PubMed to identify studies assessing the human oocyte transcriptome following ART interventions, or in the context of maternal aging, suboptimal lifestyle, or reproductive health issues.</p><p><strong>Outcomes: </strong>ART success is susceptible to external factors, maternal aging, lifestyle factors (smoking, BMI), and infertility due to endometriosis or polycystic ovary syndrome. Indeed, all of these are likely to increase oxidative stress and alter mitochondrial processes in the foreground. Concerning ART techniques themselves, there is evidence that different ovarian stimulation regimens shape the oocyte transcriptome. The perturbation of processes related to the mitochondrion, oxidative phosphorylation, and metabolism is observed with IVM. Cryopreservation might dysregulate genes belonging to transcriptional regulation, ubiquitination, cell cycle, and oocyte growth pathways. For other ART laboratory factors such as temperature, oxygen tension, air pollution, and light, the evidence remains scarce. Focusing on genes involved in chromatin-based processes such as DNA methylation, heterochromatin modulation, histone modification, and chromatin remodeling complexes, but also genomic imprinting, we observed systematic dysregulation of such genes either after ART intervention or lifestyle exposure, as well as due to internal factors such as maternal aging and reproductive diseases. Alteration in the expression of such epigenetic regulators may be a common mechanism linked to adverse oocyte environments, explaining global transcriptomic modifications.</p><p><strong>Wider implications: </strong>Many IVF factors and additional external factors have the potential to impair oocyte transcriptomic integrity, which might not be innocuous for the developing embryo. Fortunately, it
背景：全世界已有数百万儿童在人工生殖技术的帮助下出生，但人工生殖技术的无害性尚未得到充分证明。多年来，评估抗逆转录病毒疗法具体效果的工作主要集中在胚胎上；然而，决定未来胚胎发育潜力的首先是卵母细胞的质量。卵巢刺激、冷冻保存和 IVM 有时是获得成熟卵母细胞的必要步骤，但它们可能会改变卵母细胞基因组的适当表达。此外，女性不孕症、环境因素和生活方式也可能对卵母细胞转录组的质量产生重大影响，从而干扰 ART 尝试的结果。目的和依据：本综述旨在确定人类卵母细胞转录组的变化是由 ART 的特定干预措施以及年龄、生殖健康问题和生活方式等内在因素引起的。我们还为今后尝试 ART 时应采取的良好做法提供了建议：在PubMed上进行了深入的文献检索，以确定评估ART干预后人类卵母细胞转录组的研究，或在母体衰老、次优生活方式或生殖健康问题的背景下进行的研究：抗逆转录病毒疗法的成功易受外部因素、孕产妇衰老、生活方式因素（吸烟、体重指数）以及子宫内膜异位症或多囊卵巢综合征导致的不孕症的影响。事实上，所有这些都有可能增加氧化应激，改变线粒体的前处理过程。关于 ART 技术本身，有证据表明不同的卵巢刺激方案会影响卵母细胞转录组。线粒体、氧化磷酸化和新陈代谢的相关过程会受到 IVM 的干扰。低温保存可能会使转录调控、泛素化、细胞周期和卵母细胞生长途径的基因失调。至于其他 ART 实验室因素，如温度、氧张力、空气污染和光照，相关证据仍然很少。我们重点研究了参与染色质过程的基因，如 DNA 甲基化、异染色质调节、组蛋白修饰和染色质重塑复合物，以及基因组印记，观察到这些基因在 ART 干预或生活方式暴露后，以及由于母体衰老和生殖疾病等内部因素引起的系统性失调。这些表观遗传调节因子表达的改变可能是与不利的卵母细胞环境相关的共同机制，从而解释了全球转录组的改变：更广泛的影响：许多试管婴儿因素和其他外部因素都有可能损害卵母细胞转录组的完整性，这对发育中的胚胎可能并非无害。幸运的是，通过调整 ART 方案或减少不良暴露，很可能会将此类失调降至最低。
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引用次数: 0
Ultrasonographic criteria in the diagnosis of polycystic ovary syndrome: a systematic review and diagnostic meta-analysis. 多囊卵巢综合征的超声诊断标准：一项系统综述和诊断荟萃分析。
IF 14.8 1区 医学 Q1 OBSTETRICS & GYNECOLOGY
Human Reproduction Update
Pub Date : 2024-01-03 DOI: 10.1093/humupd/dmad027
Jeffrey Pea, Jahnay Bryan, Cynthia Wan, Alexis L Oldfield, Kiran Ganga, Faith E Carter, Lynn M Johnson, Marla E Lujan
<p><strong>Background: </strong>Polycystic ovary morphology (PCOM) on ultrasonography is considered as a cardinal feature of polycystic ovarian syndrome (PCOS). Its relevance as a diagnostic criterion for PCOS was reaffirmed in the most recent International Evidence-Based Guideline for the Assessment and Management of PCOS. However, there remains a lack of clarity regarding the best practices and specific ultrasonographic markers to define PCOM.</p><p><strong>Objective and rationale: </strong>The aim of this systematic review and diagnostic meta-analysis was to assess the diagnostic accuracy of various ultrasonographic features of ovarian morphology in the diagnosis of PCOS.</p><p><strong>Search methods: </strong>Relevant studies published from 1 January 1990 to 12 June 2023 were identified by a systematic search in PubMed, Web of Science, Scopus, CINAHL, and CENTRAL. Studies that generated diagnostic accuracy measures (e.g. proposed thresholds, sensitivity, specificity) for PCOS using the following ultrasonographic markers met criteria for inclusion: follicle number per ovary (FNPO) or per single cross-section (FNPS), ovarian volume (OV), and stromal features. Studies on pregnant or post-menopausal women were excluded. Risk of bias and applicability assessment for diagnostic test accuracy studies were determined using the QUADAS-2 and QUADAS-C tool for a single index test or between multiple index tests, respectively. Diagnostic meta-analysis was conducted using a bivariate model of pooled sensitivity and specificity, and visualized using forest plots and summary receiver-operating characteristic (SROC) curves.</p><p><strong>Outcomes: </strong>From a total of 2197 records initially identified, 31 studies were included. Data from five and two studies were excluded from the meta-analysis due to duplicate study populations or limited data for the index test, leaving 24 studies. Pooled results of 20 adult studies consisted of 3883 control participants and 3859 individuals with PCOS. FNPO was the most accurate diagnostic marker (sensitivity: 84%, CI: 81-87%; specificity: 91%, CI: 86-94%; AUC: 0.905) in adult women. OV and FNPS had similar pooled sensitivities (OV: 81%, CI: 76-86%; FNPS: 81%, CI: 70-89%) but inferior pooled specificities (OV: 81%, CI: 75-86%; FNPS: 83%, CI: 75-88%) and AUCs (OV: 0.856; FNPS: 0.870) compared to FNPO. Pooled results from four adolescent studies consisting of 210 control participants and 268 girls with PCOS suggested that OV may be a robust ultrasonographic marker for PCOS diagnosis albeit the current evidence remains limited. The majority of the studies had high risk of bias for the patient selection (e.g. lack of randomized/consecutive patient selection) and index test (e.g. lack of pre-proposed thresholds for comparison) domains across all ultrasonographic markers. As such, diagnostic meta-analysis was unable to determine the most accurate cutoff for ultrasonographic markers to diagnose PCOS. Subgroup analysis suggest
背景：多囊卵巢形态（PCOM）超声检查被认为是多囊卵巢综合征（PCOS）的主要特征。最新的《国际多囊卵巢综合征评估和管理循证指南》重申了其作为多囊卵巢综合症诊断标准的相关性。然而目前尚不清楚定义多囊卵巢综合征的最佳实践和特定超声标记物。目的和原理：本系统综述和诊断荟萃分析的目的是评估卵巢形态的各种超声特征在多囊卵巢综合症诊断中的准确性。检索方法：1990年1月1日至6月12日发表的相关研究2023个是通过PubMed、Web of Science、Scopus、CINAHL和CENTRAL的系统搜索确定的。使用以下超声标记物生成多囊卵巢综合征诊断准确性指标（如拟议阈值、敏感性、特异性）的研究符合纳入标准：每个卵巢的卵泡数（FNPO）或单个横截面的卵泡数、卵巢体积（OV）和基质特征。排除了对孕妇或绝经后妇女的研究。诊断测试准确性研究的偏倚风险和适用性评估分别使用单指标测试或多指标测试之间的QUADAS-2和QUADAS-C工具确定。使用敏感性和特异性合并的双变量模型进行诊断荟萃分析，并使用森林图和受试者操作特征汇总曲线（SROC）进行可视化。结果：从最初确定的2197份记录中，纳入了31项研究。由于研究人群重复或指数测试数据有限，五项和两项研究的数据被排除在荟萃分析之外，剩下24项研究。20项成人研究的汇总结果包括3883名对照参与者和3859名多囊卵巢综合征患者。FNPO是成年女性最准确的诊断标志物（敏感性：84%，CI:81-87%；特异性：91%，CI:86-94%；AUC:0.905）。OV和FNPS具有相似的合并敏感性（OV:81%，CI:76-86%；FNPS:81%，CI：70-89%），但与FNPO相比，合并特异性较差（OV:80%，CI:75-86%；FNPS-83%，CI:75-98%）和AUC（OV:0.856；FNPS:0.870）。由210名对照参与者和268名多囊卵巢综合征女孩组成的四项青少年研究的汇总结果表明，尽管目前的证据仍然有限，但OV可能是多囊卵巢综合症诊断的有力超声标记。大多数研究在所有超声标记物的患者选择（例如缺乏随机/连续的患者选择）和指标测试（例如缺乏预先提出的比较阈值）领域存在高偏倚风险。因此，诊断荟萃分析无法确定超声标记物诊断多囊卵巢综合征的最准确界限。亚组分析表明，基于先前提出的诊断阈值、年龄、BMI或技术的分层并不能解释研究中观察到的诊断准确性的异质性。使用鹿特丹标准诊断多囊卵巢综合征的研究提高了FNPO的敏感性。与亚洲研究（FNPO：敏感性）和欧洲研究（OV：特异性、诊断比值比和阳性似然比）相比，北美研究的诊断准确性较低。诊断准确性的地理差异可能是由于不同地区PCOS组的年龄、BMI和诊断标准的差异。更广泛的意义：这项诊断荟萃分析支持将FNPO作为成年女性多囊卵巢综合征超声诊断的金标准。OV和FNPS在无法准确获得窦卵泡总数的情况下提供了替代方案。随着更多的数据可用，我们的发现支持了青少年多囊卵巢综合征超声证据的潜力。亚组分析表明，有必要调查地理差异对多囊卵巢综合征表型的任何相对贡献。这些发现可能为制定PCOM的标准化定义和更准确的PCOS超声评估策略和最佳实践提供基础。
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引用次数: 0
Endometrial receptivity in women of advanced age: an underrated factor in infertility. 高龄妇女子宫内膜容受性:一个被低估的不孕症因素。
IF 14.8 1区 医学 Q1 OBSTETRICS & GYNECOLOGY
Human Reproduction Update
Pub Date : 2023-11-02 DOI: 10.1093/humupd/dmad019
Amruta D S Pathare, Marina Loid, Merli Saare, Sebastian Brusell Gidlöf, Masoud Zamani Esteki, Ganesh Acharya, Maire Peters, Andres Salumets

Background: Modern lifestyle has led to an increase in the age at conception. Advanced age is one of the critical risk factors for female-related infertility. It is well known that maternal age positively correlates with the deterioration of oocyte quality and chromosomal abnormalities in oocytes and embryos. The effect of age on endometrial function may be an equally important factor influencing implantation rate, pregnancy rate, and overall female fertility. However, there are only a few published studies on this topic, suggesting that this area has been under-explored. Improving our knowledge of endometrial aging from the biological (cellular, molecular, histological) and clinical perspectives would broaden our understanding of the risks of age-related female infertility.

Objective and rationale: The objective of this narrative review is to critically evaluate the existing literature on endometrial aging with a focus on synthesizing the evidence for the impact of endometrial aging on conception and pregnancy success. This would provide insights into existing gaps in the clinical application of research findings and promote the development of treatment options in this field.

Search methods: The review was prepared using PubMed (Medline) until February 2023 with the keywords such as 'endometrial aging', 'receptivity', 'decidualization', 'hormone', 'senescence', 'cellular', 'molecular', 'methylation', 'biological age', 'epigenetic', 'oocyte recipient', 'oocyte donation', 'embryo transfer', and 'pregnancy rate'. Articles in a language other than English were excluded.

Outcomes: In the aging endometrium, alterations occur at the molecular, cellular, and histological levels suggesting that aging has a negative effect on endometrial biology and may impair endometrial receptivity. Additionally, advanced age influences cellular senescence, which plays an important role during the initial phase of implantation and is a major obstacle in the development of suitable senolytic agents for endometrial aging. Aging is also accountable for chronic conditions associated with inflammaging, which eventually can lead to increased pro-inflammation and tissue fibrosis. Furthermore, advanced age influences epigenetic regulation in the endometrium, thus altering the relation between its epigenetic and chronological age. The studies in oocyte donation cycles to determine the effect of age on endometrial receptivity with respect to the rates of implantation, clinical pregnancy, miscarriage, and live birth have revealed contradictory inferences indicating the need for future research on the mechanisms and corresponding causal effects of women's age on endometrial receptivity.

Wider implications: Increasing age can be accountable for female infertility and IVF failures. Based on the complied observations and synthesized conclusions in this review, advanced age h

背景：现代生活方式导致受孕年龄的增加。高龄是女性不育的重要危险因素之一。众所周知，母亲年龄与卵母细胞质量恶化以及卵母细胞和胚胎染色体异常呈正相关。年龄对子宫内膜功能的影响可能是影响植入率、妊娠率和女性整体生育能力的一个同样重要的因素。然而，只有少数已发表的关于这一主题的研究表明，这一领域的探索不足。从生物学（细胞、分子、组织学）和临床角度提高我们对子宫内膜衰老的认识，将拓宽我们对年龄相关女性不孕风险的理解。目的和理由：这篇叙述性综述的目的是批判性地评估现有的关于子宫内膜衰老的文献，重点是综合子宫内膜衰老对受孕和妊娠成功影响的证据。这将深入了解研究结果临床应用中存在的差距，并促进该领域治疗方案的发展。搜索方法：该综述使用PubMed（Medline）编制，直到2023年2月，关键词为“子宫内膜老化”、“接受性”、“蜕膜化”、“激素”、“衰老”、“细胞”、“分子”、“甲基”、“生物年龄”、“表观遗传学”、“卵母细胞受体”、“卵子捐赠”、“胚胎移植”和“妊娠率”。英语以外的其他语言的文章被排除在外。结果：在衰老的子宫内膜中，在分子、细胞和组织学水平上发生了变化，这表明衰老对子宫内膜生物学有负面影响，并可能损害子宫内膜的接受能力。此外，高龄会影响细胞衰老，而细胞衰老在植入的初始阶段起着重要作用，也是开发适合子宫内膜衰老的senolytic药物的主要障碍。衰老也是与炎症相关的慢性疾病的原因，炎症最终会导致促炎症和组织纤维化的增加。此外，高龄会影响子宫内膜的表观遗传学调节，从而改变其表观遗传学和实际年龄之间的关系。关于卵母细胞捐献周期的研究，旨在确定年龄对子宫内膜容受性的影响，包括植入率、临床妊娠率、流产率和活产率，这些研究揭示了相互矛盾的推论，表明未来有必要研究女性年龄对内膜容受力的机制和相应的因果影响。更广泛的影响：年龄的增长可能是女性不孕和试管婴儿失败的原因。根据本综述中的观察结果和综合结论，高龄已被证明对子宫内膜功能有负面影响。这些信息可以为未来的研究提供建议，重点是与年龄相关的细胞衰老的分子机制、细胞组成和与子宫内膜衰老相关的转录组学变化。此外，还需要进一步的前瞻性研究来探索新出现的治疗选择，例如可以靶向子宫内膜衰老而不影响蜕膜化的senolytic药物。此外，以卵母细胞捐献周期为重点的临床试验方案将有助于了解子宫内膜衰老对妊娠结局的直接临床影响。
{"title":"Endometrial receptivity in women of advanced age: an underrated factor in infertility.","authors":"Amruta D S Pathare, Marina Loid, Merli Saare, Sebastian Brusell Gidlöf, Masoud Zamani Esteki, Ganesh Acharya, Maire Peters, Andres Salumets","doi":"10.1093/humupd/dmad019","DOIUrl":"10.1093/humupd/dmad019","url":null,"abstract":"<p><strong>Background: </strong>Modern lifestyle has led to an increase in the age at conception. Advanced age is one of the critical risk factors for female-related infertility. It is well known that maternal age positively correlates with the deterioration of oocyte quality and chromosomal abnormalities in oocytes and embryos. The effect of age on endometrial function may be an equally important factor influencing implantation rate, pregnancy rate, and overall female fertility. However, there are only a few published studies on this topic, suggesting that this area has been under-explored. Improving our knowledge of endometrial aging from the biological (cellular, molecular, histological) and clinical perspectives would broaden our understanding of the risks of age-related female infertility.</p><p><strong>Objective and rationale: </strong>The objective of this narrative review is to critically evaluate the existing literature on endometrial aging with a focus on synthesizing the evidence for the impact of endometrial aging on conception and pregnancy success. This would provide insights into existing gaps in the clinical application of research findings and promote the development of treatment options in this field.</p><p><strong>Search methods: </strong>The review was prepared using PubMed (Medline) until February 2023 with the keywords such as 'endometrial aging', 'receptivity', 'decidualization', 'hormone', 'senescence', 'cellular', 'molecular', 'methylation', 'biological age', 'epigenetic', 'oocyte recipient', 'oocyte donation', 'embryo transfer', and 'pregnancy rate'. Articles in a language other than English were excluded.</p><p><strong>Outcomes: </strong>In the aging endometrium, alterations occur at the molecular, cellular, and histological levels suggesting that aging has a negative effect on endometrial biology and may impair endometrial receptivity. Additionally, advanced age influences cellular senescence, which plays an important role during the initial phase of implantation and is a major obstacle in the development of suitable senolytic agents for endometrial aging. Aging is also accountable for chronic conditions associated with inflammaging, which eventually can lead to increased pro-inflammation and tissue fibrosis. Furthermore, advanced age influences epigenetic regulation in the endometrium, thus altering the relation between its epigenetic and chronological age. The studies in oocyte donation cycles to determine the effect of age on endometrial receptivity with respect to the rates of implantation, clinical pregnancy, miscarriage, and live birth have revealed contradictory inferences indicating the need for future research on the mechanisms and corresponding causal effects of women's age on endometrial receptivity.</p><p><strong>Wider implications: </strong>Increasing age can be accountable for female infertility and IVF failures. Based on the complied observations and synthesized conclusions in this review, advanced age h","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"773-793"},"PeriodicalIF":14.8,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10195806","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
The pathophysiological role of estrogens in the initial stages of pregnancy: molecular mechanisms and clinical implications for pregnancy outcome from the periconceptional period to end of the first trimester. 雌激素在妊娠初期的病理生理作用:从围孕期到妊娠早期结束的妊娠结局的分子机制和临床意义。
IF 14.8 1区 医学 Q1 OBSTETRICS & GYNECOLOGY
Human Reproduction Update
Pub Date : 2023-11-02 DOI: 10.1093/humupd/dmad016
F Parisi, C Fenizia, A Introini, A Zavatta, C Scaccabarozzi, M Biasin, V Savasi
<p><strong>Background: </strong>Estrogens regulate disparate female physiological processes, thus ensuring reproduction. Altered estrogen levels and signaling have been associated with increased risks of pregnancy failure and complications, including hypertensive disorders and low birthweight babies. However, the role of estrogens in the periconceptional period and early pregnancy is still understudied.</p><p><strong>Objective and rationale: </strong>This review aims to summarize the current evidence on the role of maternal estrogens during the periconceptional period and the first trimester of pregnancies conceived naturally and following ART. Detailed molecular mechanisms and related clinical impacts are extensively described.</p><p><strong>Search methods: </strong>Data for this narrative review were independently identified by seven researchers on Pubmed and Embase databases. The following keywords were selected: 'estrogens' OR 'estrogen level(s)' OR 'serum estradiol' OR 'estradiol/estrogen concentration', AND 'early pregnancy' OR 'first trimester of pregnancy' OR 'preconceptional period' OR 'ART' OR 'In Vitro Fertilization (IVF)' OR 'Embryo Transfer' OR 'Frozen Embryo Transfer' OR 'oocyte donation' OR 'egg donation' OR 'miscarriage' OR 'pregnancy outcome' OR 'endometrium'.</p><p><strong>Outcomes: </strong>During the periconceptional period (defined here as the critical time window starting 1 month before conception), estrogens play a crucial role in endometrial receptivity, through the activation of paracrine/autocrine signaling. A derailed estrogenic milieu within this period seems to be detrimental both in natural and ART-conceived pregnancies. Low estrogen levels are associated with non-conception cycles in natural pregnancies. On the other hand, excessive supraphysiologic estrogen concentrations at time of the LH peak correlate with lower live birth rates and higher risks of pregnancy complications. In early pregnancy, estrogen plays a massive role in placentation mainly by modulating angiogenic factor expression-and in the development of an immune-tolerant uterine micro-environment by remodeling the function of uterine natural killer and T-helper cells. Lower estrogen levels are thought to trigger abnormal placentation in naturally conceived pregnancies, whereas an estrogen excess seems to worsen pregnancy development and outcomes.</p><p><strong>Wider implications: </strong>Most current evidence available endorses a relation between periconceptional and first trimester estrogen levels and pregnancy outcomes, further depicting an optimal concentration range to optimize pregnancy success. However, how estrogens co-operate with other factors in order to maintain a fine balance between local tolerance towards the developing fetus and immune responses to pathogens remains elusive. Further studies are highly warranted, also aiming to identify the determinants of estrogen response and biomarkers for personalized estrogen administration regimens
背景：雌激素调节不同的女性生理过程，从而确保生殖。雌激素水平和信号传导的改变与妊娠失败和并发症的风险增加有关，包括高血压疾病和低出生体重婴儿。然而，雌激素在围产期和早孕期的作用仍然研究不足。目的和原理：这篇综述旨在总结目前关于母体雌激素在自然受孕和ART后妊娠的围产期和前三个月的作用的证据。详细的分子机制和相关的临床影响被广泛描述。搜索方法：这篇叙述性综述的数据由七名研究人员在Pubmed和Embase数据库中独立确定。选择以下关键词：“雌激素”或“雌激素水平”或“血清雌二醇”或“雌二醇/雌激素浓度”，AND“早孕”或“妊娠早期”或“受孕期”或“ART”或“体外受精（IVF）”或“胚胎移植”或“冷冻胚胎移植”、“卵子捐赠”或“流产”或“怀孕结果”或“子宫内膜” 受孕前一个月），雌激素通过激活旁分泌/自分泌信号在子宫内膜容受性中发挥着至关重要的作用。在这段时间内，雌激素环境的紊乱似乎对自然妊娠和ART妊娠都是有害的。雌激素水平低与自然妊娠的非受孕周期有关。另一方面，LH峰值时超生理雌激素浓度过高与较低的活产率和较高的妊娠并发症风险相关。在妊娠早期，雌激素主要通过调节血管生成因子的表达在胎盘形成中发挥重要作用，并通过重塑子宫自然杀伤细胞和辅助T细胞的功能在免疫耐受性子宫微环境的形成中发挥巨大作用。在自然受孕的妊娠中，雌激素水平较低被认为会引发异常胎盘形成，而雌激素过量似乎会恶化妊娠发育和结局。更广泛的含义：目前大多数可用的证据都支持孕周和孕早期雌激素水平与妊娠结局之间的关系，进一步描述了优化妊娠成功率的最佳浓度范围。然而，雌激素如何与其他因素合作，以在对发育中的胎儿的局部耐受性和对病原体的免疫反应之间保持良好的平衡，仍然难以捉摸。进一步的研究是非常有必要的，也旨在确定雌激素反应的决定因素和ART中个性化雌激素给药方案的生物标志物。
{"title":"The pathophysiological role of estrogens in the initial stages of pregnancy: molecular mechanisms and clinical implications for pregnancy outcome from the periconceptional period to end of the first trimester.","authors":"F Parisi, C Fenizia, A Introini, A Zavatta, C Scaccabarozzi, M Biasin, V Savasi","doi":"10.1093/humupd/dmad016","DOIUrl":"10.1093/humupd/dmad016","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Estrogens regulate disparate female physiological processes, thus ensuring reproduction. Altered estrogen levels and signaling have been associated with increased risks of pregnancy failure and complications, including hypertensive disorders and low birthweight babies. However, the role of estrogens in the periconceptional period and early pregnancy is still understudied.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective and rationale: &lt;/strong&gt;This review aims to summarize the current evidence on the role of maternal estrogens during the periconceptional period and the first trimester of pregnancies conceived naturally and following ART. Detailed molecular mechanisms and related clinical impacts are extensively described.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Search methods: &lt;/strong&gt;Data for this narrative review were independently identified by seven researchers on Pubmed and Embase databases. The following keywords were selected: 'estrogens' OR 'estrogen level(s)' OR 'serum estradiol' OR 'estradiol/estrogen concentration', AND 'early pregnancy' OR 'first trimester of pregnancy' OR 'preconceptional period' OR 'ART' OR 'In Vitro Fertilization (IVF)' OR 'Embryo Transfer' OR 'Frozen Embryo Transfer' OR 'oocyte donation' OR 'egg donation' OR 'miscarriage' OR 'pregnancy outcome' OR 'endometrium'.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Outcomes: &lt;/strong&gt;During the periconceptional period (defined here as the critical time window starting 1 month before conception), estrogens play a crucial role in endometrial receptivity, through the activation of paracrine/autocrine signaling. A derailed estrogenic milieu within this period seems to be detrimental both in natural and ART-conceived pregnancies. Low estrogen levels are associated with non-conception cycles in natural pregnancies. On the other hand, excessive supraphysiologic estrogen concentrations at time of the LH peak correlate with lower live birth rates and higher risks of pregnancy complications. In early pregnancy, estrogen plays a massive role in placentation mainly by modulating angiogenic factor expression-and in the development of an immune-tolerant uterine micro-environment by remodeling the function of uterine natural killer and T-helper cells. Lower estrogen levels are thought to trigger abnormal placentation in naturally conceived pregnancies, whereas an estrogen excess seems to worsen pregnancy development and outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Wider implications: &lt;/strong&gt;Most current evidence available endorses a relation between periconceptional and first trimester estrogen levels and pregnancy outcomes, further depicting an optimal concentration range to optimize pregnancy success. However, how estrogens co-operate with other factors in order to maintain a fine balance between local tolerance towards the developing fetus and immune responses to pathogens remains elusive. Further studies are highly warranted, also aiming to identify the determinants of estrogen response and biomarkers for personalized estrogen administration regimens","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"699-720"},"PeriodicalIF":14.8,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9677177","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
Endometrial scratching in women undergoing IVF/ICSI: an individual participant data meta-analysis. 接受IVF/ICSI的女性子宫内膜刮伤:个体参与者数据荟萃分析。
IF 14.8 1区 医学 Q1 OBSTETRICS & GYNECOLOGY
Human Reproduction Update
Pub Date : 2023-11-02 DOI: 10.1093/humupd/dmad014
Nienke E van Hoogenhuijze, Gemma Lahoz Casarramona, Sarah Lensen, Cindy Farquhar, Mohan S Kamath, Aleyamma T Kunjummen, Nick Raine-Fenning, Sine Berntsen, Anja Pinborg, Shari Mackens, Zeynep Ozturk Inal, Ernest H Y Ng, Jennifer S M Mak, Sachin A Narvekar, Wellington P Martins, Mia Steengaard Olesen, Helen L Torrance, Ben W Mol, Marinus J C Eijkemans, Rui Wang, Frank J M Broekmans
<p><strong>Background: </strong>In IVF/ICSI treatment, the process of embryo implantation is the success rate-limiting step. Endometrial scratching has been suggested to improve this process, but it is unclear if this procedure increases the chance of implantation and live birth (LB) and, if so, for whom, and how the scratch should be performed.</p><p><strong>Objective and rationale: </strong>This individual participant data meta-analysis (IPD-MA) aims to answer the question of whether endometrial scratching in women undergoing IVF/ICSI influences the chance of a LB, and whether this effect is different in specific subgroups of women. After its incidental discovery in 2000, endometrial scratching has been suggested to improve embryo implantation. Numerous randomized controlled trials (RCTs) have been conducted, showing contradicting results. Conventional meta-analyses were limited by high within- and between-study heterogeneity, small study samples, and a high risk of bias for many of the trials. Also, the data integrity of several trials have been questioned. Thus, despite numerous RCTs and a multitude of conventional meta-analyses, no conclusion on the clinical effectiveness of endometrial scratching could be drawn. An IPD-MA approach is able to overcome many of these problems because it allows for increased uniformity of outcome definitions, can filter out studies with data integrity concerns, enables a more precise estimation of the true treatment effect thanks to adjustment for participant characteristics and not having to make the assumptions necessary in conventional meta-analyses, and because it allows for subgroup analysis.</p><p><strong>Search methods: </strong>A systematic literature search identified RCTs on endometrial scratching in women undergoing IVF/ICSI. Authors of eligible studies were invited to share original data for this IPD-MA. Studies were assessed for risk of bias (RoB) and integrity checks were performed. The primary outcome was LB, with a one-stage intention to treat (ITT) as the primary analysis. Secondary analyses included as treated (AT), and the subset of women that underwent an embryo transfer (AT+ET). Treatment-covariate interaction for specific participant characteristics was analyzed in AT+ET.</p><p><strong>Outcomes: </strong>Out of 37 published and 15 unpublished RCTs (7690 participants), 15 RCTs (14 published, one unpublished) shared data. After data integrity checks, we included 13 RCTs (12 published, one unpublished) representing 4112 participants. RoB was evaluated as 'low' for 10/13 RCTs. The one-stage ITT analysis for scratch versus no scratch/sham showed an improvement of LB rates (odds ratio (OR) 1.29 [95% CI 1.02-1.64]). AT, AT+ET, and low-RoB-sensitivity analyses yielded similar results (OR 1.22 [95% CI 0.96-1.54]; OR 1.25 [95% CI 0.99-1.57]; OR 1.26 [95% CI 1.03-1.55], respectively). Treatment-covariate interaction analysis showed no evidence of interaction with age, number of previous failed embryo
背景：在IVF/ICSI治疗中，胚胎植入过程是限制成功率的步骤。有人建议子宫内膜刮伤可以改善这一过程，但目前尚不清楚这种手术是否会增加植入和活产（LB）的机会，如果会，应该为谁以及如何进行刮伤。目的和理由：这项个体参与者数据荟萃分析（IPD-MA）旨在回答接受IVF/ICSI的女性子宫内膜抓挠是否会影响LB的机会，以及这种影响在特定的女性亚组中是否不同的问题。在2000年偶然发现后，子宫内膜刮伤被认为可以改善胚胎植入。已经进行了大量的随机对照试验，结果相互矛盾。传统的荟萃分析受到研究内部和研究之间高度异质性、研究样本小以及许多试验的高偏倚风险的限制。此外，一些试验的数据完整性也受到质疑。因此，尽管进行了大量的随机对照试验和常规荟萃分析，但无法得出子宫内膜刮伤临床有效性的结论。IPD-MA方法能够克服其中的许多问题，因为它允许增加结果定义的一致性，可以过滤出有数据完整性问题的研究，由于对参与者特征的调整，能够更精确地估计真实的治疗效果，并且不必在传统的荟萃分析中做出必要的假设，并且因为它允许亚组分析。检索方法：系统文献检索确定了接受IVF/ICSI的女性子宫内膜刮伤的随机对照试验。邀请符合条件的研究的作者分享本IPD-MA的原始数据。对偏倚风险（RoB）进行了评估，并进行了完整性检查。主要结果为LB，以一阶段意向治疗（ITT）作为主要分析。二次分析包括治疗时（AT）和接受胚胎移植的妇女子集（AT+ET）。在AT+ET中分析了特定参与者特征的治疗协变量相互作用。结果：在37项已发表和15项未发表的随机对照试验中（7690名参与者），15项随机对照试验（14项已发表，1项未发表）共享数据。在数据完整性检查后，我们纳入了13项随机对照试验（12项已发表，1项未发表），代表4112名参与者。10/13随机对照试验的RoB评价为“低”。抓伤与不抓伤/假手术的一阶段ITT分析显示LB发生率有所改善（比值比（OR）1.29[95%CI 1.02-1.64]）。AT、AT+ET和低RoB敏感性分析得出了相似的结果（分别为OR 1.22[95%CI 0.96-1.54]；OR 1.25[95%CI 0.99-1.57]；OR 1.26[95%CI 1.03-1.55]）。治疗协变量相互作用分析显示，没有证据表明与年龄、既往胚胎移植失败次数、治疗类型或不孕原因存在相互作用。更广泛的含义：这是第一个基于4000多名参与者的IPD的荟萃分析，它表明子宫内膜刮伤可能会提高接受IVF/ICSI的女性的LB率。年龄、既往胚胎移植失败次数、治疗类型和不孕原因的亚组分析无法确定子宫内膜刮伤表现较好或较差的亚组。子宫内膜刮伤的时机可能对其有效性起到一定作用。应谨慎考虑在临床实践中使用子宫内膜刮伤，这意味着应就证据水平和不确定性向患者提供适当的咨询。
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引用次数: 0
Assessing the influence of preconception diet on female fertility: a systematic scoping review of observational studies. 评估孕前饮食对女性生育能力的影响:观察性研究的系统范围综述。
IF 14.8 1区 医学 Q1 OBSTETRICS & GYNECOLOGY
Human Reproduction Update
Pub Date : 2023-11-02 DOI: 10.1093/humupd/dmad018
Simon Alesi, Nahal Habibi, Thais Rasia Silva, Nicole Cheung, Sophia Torkel, Chau Thien Tay, Alejandra Quinteros, Hugo Winter, Helena Teede, Aya Mousa, Jessica A Grieger, Lisa J Moran

Background: Preconception diet is a proposed modifiable risk factor for infertility. However, there is no official guidance for women in the preconception period as to which dietary approaches may improve fertility.

Objective and rationale: A comprehensive synthesis of the relevant evidence is key to determine the potentially effective dietary patterns and components as well as evidence gaps, and to provide information for nutritional recommendations for couples planning a pregnancy.

Search methods: In this systematic scoping review, four electronic databases (Medline and EMBASE via Ovid processing, CAB Direct, and CINAHL via EBSCO) were searched for observational studies (prospective and retrospective cohort, cross-sectional, and case-control studies) from inception to 27 September 2021. Eligible studies included women of reproductive age during the preconception period, and evaluated exposures related to preconception diet and outcomes related to fertility. Results were synthesized using a descriptive approach.

Outcomes: A total of 36 studies were eligible for inclusion (31 prospective, 3 cross-sectional, and 2 case-control studies) and were published between 2007 and 2022. Of the assessed dietary exposures, increased adherence to the Mediterranean diet displayed the strongest and most consistent association with improved clinical pregnancy rates. Reducing trans fatty acids (TFAs), saturated fatty acids, and discretionary food intake (fast food and sugar-sweetened beverages) were associated with improvements in live birth, clinical pregnancy rates, and related ART outcomes. The dietary components of seafood, dairy, and soy demonstrated inconsistent findings across the few included studies.

Wider implications: Due to heterogeneity and the limited available literature on most exposures, there is insufficient evidence to support any specific dietary approach for improving fertility. However, following some of the dietary approaches outlined in this review (anti-inflammatory diets, reducing TFA, and discretionary food intake) are consistent with broad healthy eating guidelines, have little to no associated risk, and offer a plausible set of possible benefits. This warrants further exploration in randomized controlled trials.

背景：孕前饮食是一种可改变的不孕风险因素。然而，对于哪些饮食方法可以提高生育能力，没有针对处于先入为主阶段的妇女的官方指导。目标和理由：全面综合相关证据是确定潜在有效的饮食模式和成分以及证据差距的关键，也是为计划怀孕的夫妇提供营养建议的关键。搜索方法：在这项系统范围界定综述中，从开始到2021年9月27日，对四个电子数据库（通过Ovid处理的Medline和EMBASE、CAB Direct和通过EBSCO的CINAHL）进行了观察性研究（前瞻性和回顾性队列、横断面和病例对照研究）的搜索。符合条件的研究包括怀孕期的育龄妇女，并评估了与怀孕饮食相关的暴露和与生育相关的结果。结果采用描述性方法进行综合。结果：共有36项研究符合入选条件（31项前瞻性研究、3项横断面研究和2项病例对照研究），于2007年至2022年间发表。在评估的饮食暴露中，对地中海饮食的依从性增加与临床妊娠率的提高表现出最强烈、最一致的相关性。减少反式脂肪酸（TFAs）、饱和脂肪酸和可自由支配的食物摄入（快餐和含糖饮料）与活产、临床妊娠率和相关ART结果的改善有关。在少数纳入的研究中，海鲜、乳制品和大豆的饮食成分显示出不一致的结果。更广泛的影响：由于异质性和关于大多数暴露的可用文献有限，没有足够的证据支持任何提高生育率的特定饮食方法。然而，遵循本综述中概述的一些饮食方法（抗炎饮食、减少TFA和可自由支配的食物摄入）符合广泛的健康饮食指南，几乎没有相关风险，并提供了一系列可能的好处。这值得在随机对照试验中进一步探索。
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引用次数: 0
Dissecting mammalian reproduction with spatial transcriptomics. 用空间转录组学解剖哺乳动物生殖。
IF 14.8 1区 医学 Q1 OBSTETRICS & GYNECOLOGY
Human Reproduction Update
Pub Date : 2023-11-02 DOI: 10.1093/humupd/dmad017
Xin Zhang, Qiqi Cao, Shreya Rajachandran, Edward J Grow, Melanie Evans, Haiqi Chen
<p><strong>Background: </strong>Mammalian reproduction requires the fusion of two specialized cells: an oocyte and a sperm. In addition to producing gametes, the reproductive system also provides the environment for the appropriate development of the embryo. Deciphering the reproductive system requires understanding the functions of each cell type and cell-cell interactions. Recent single-cell omics technologies have provided insights into the gene regulatory network in discrete cellular populations of both the male and female reproductive systems. However, these approaches cannot examine how the cellular states of the gametes or embryos are regulated through their interactions with neighboring somatic cells in the native tissue environment owing to tissue disassociations. Emerging spatial omics technologies address this challenge by preserving the spatial context of the cells to be profiled. These technologies hold the potential to revolutionize our understanding of mammalian reproduction.</p><p><strong>Objective and rationale: </strong>We aim to review the state-of-the-art spatial transcriptomics (ST) technologies with a focus on highlighting the novel biological insights that they have helped to reveal about the mammalian reproductive systems in the context of gametogenesis, embryogenesis, and reproductive pathologies. We also aim to discuss the current challenges of applying ST technologies in reproductive research and provide a sneak peek at what the field of spatial omics can offer for the reproduction community in the years to come.</p><p><strong>Search methods: </strong>The PubMed database was used in the search for peer-reviewed research articles and reviews using combinations of the following terms: 'spatial omics', 'fertility', 'reproduction', 'gametogenesis', 'embryogenesis', 'reproductive cancer', 'spatial transcriptomics', 'spermatogenesis', 'ovary', 'uterus', 'cervix', 'testis', and other keywords related to the subject area. All relevant publications until April 2023 were critically evaluated and discussed.</p><p><strong>Outcomes: </strong>First, an overview of the ST technologies that have been applied to studying the reproductive systems was provided. The basic design principles and the advantages and limitations of these technologies were discussed and tabulated to serve as a guide for researchers to choose the best-suited technologies for their own research. Second, novel biological insights into mammalian reproduction, especially human reproduction revealed by ST analyses, were comprehensively reviewed. Three major themes were discussed. The first theme focuses on genes with non-random spatial expression patterns with specialized functions in multiple reproductive systems; The second theme centers around functionally interacting cell types which are often found to be spatially clustered in the reproductive tissues; and the thrid theme discusses pathological states in reproductive systems which are often associated with unique
背景：哺乳动物的生殖需要两种特殊细胞的融合：卵母细胞和精子。除了产生配子外，生殖系统还为胚胎的适当发育提供了环境。解读生殖系统需要了解每种细胞类型的功能和细胞间的相互作用。最近的单细胞组学技术为男性和女性生殖系统的离散细胞群体中的基因调控网络提供了见解。然而，这些方法无法检测配子或胚胎的细胞状态是如何通过与天然组织环境中相邻体细胞的相互作用来调节的，这是由于组织分离。新兴的空间组学技术通过保留待分析细胞的空间背景来应对这一挑战。这些技术有可能彻底改变我们对哺乳动物繁殖的理解。目的和原理：我们旨在回顾最先进的空间转录组学（ST）技术，重点强调它们在配子发生、胚胎发生和生殖病理学的背景下帮助揭示的关于哺乳动物生殖系统的新生物学见解。我们还旨在讨论将ST技术应用于生殖研究的当前挑战，并窥探空间组学领域在未来几年可以为生殖界提供什么。搜索方法：使用PubMed数据库搜索同行评议的研究文章和评论，使用以下术语的组合：“空间组学”、“生育能力”、“生殖”、“配子发生”、“胚胎发生”、《癌症生殖》、“空间转录组学”，“精子发生”，“卵巢”、“子宫”、“宫颈”、“睾丸”和其他与主题领域相关的关键词。对截至2023年4月的所有相关出版物进行了严格评估和讨论。结果：首先，概述了已应用于生殖系统研究的ST技术。讨论并列出了这些技术的基本设计原则以及优点和局限性，以指导研究人员选择最适合自己研究的技术。其次，对ST分析揭示的哺乳动物繁殖，特别是人类繁殖的新生物学见解进行了全面综述。讨论了三个主要主题。第一个主题关注在多个生殖系统中具有特殊功能的具有非随机空间表达模式的基因；第二个主题围绕功能相互作用的细胞类型展开，这些细胞类型通常在生殖组织中空间聚集；第三个主题讨论了生殖系统中的病理状态，这些状态通常与独特的细胞微环境有关。最后，强调了当前应用ST技术研究哺乳动物繁殖的实验和计算挑战，并提供了应对这些挑战的潜在解决方案。讨论了空间组学技术的未来发展方向，以及它们将如何造福于人类生殖领域，包括细胞和组织动力学的捕获、多模式分子图谱和基因扰动的空间表征。更广泛的含义：与单细胞技术一样，空间组学技术在为哺乳动物繁殖提供重要而新颖的见解方面具有巨大的潜力。我们的综述总结了ST技术提供的这些新的生物学见解，同时揭示了未来的发展。我们的综述为生殖生物学家和临床医生提供了ST技术的最新进展。它还可以促进在基础和临床生殖研究中采用尖端的空间技术。
{"title":"Dissecting mammalian reproduction with spatial transcriptomics.","authors":"Xin Zhang, Qiqi Cao, Shreya Rajachandran, Edward J Grow, Melanie Evans, Haiqi Chen","doi":"10.1093/humupd/dmad017","DOIUrl":"10.1093/humupd/dmad017","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Mammalian reproduction requires the fusion of two specialized cells: an oocyte and a sperm. In addition to producing gametes, the reproductive system also provides the environment for the appropriate development of the embryo. Deciphering the reproductive system requires understanding the functions of each cell type and cell-cell interactions. Recent single-cell omics technologies have provided insights into the gene regulatory network in discrete cellular populations of both the male and female reproductive systems. However, these approaches cannot examine how the cellular states of the gametes or embryos are regulated through their interactions with neighboring somatic cells in the native tissue environment owing to tissue disassociations. Emerging spatial omics technologies address this challenge by preserving the spatial context of the cells to be profiled. These technologies hold the potential to revolutionize our understanding of mammalian reproduction.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective and rationale: &lt;/strong&gt;We aim to review the state-of-the-art spatial transcriptomics (ST) technologies with a focus on highlighting the novel biological insights that they have helped to reveal about the mammalian reproductive systems in the context of gametogenesis, embryogenesis, and reproductive pathologies. We also aim to discuss the current challenges of applying ST technologies in reproductive research and provide a sneak peek at what the field of spatial omics can offer for the reproduction community in the years to come.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Search methods: &lt;/strong&gt;The PubMed database was used in the search for peer-reviewed research articles and reviews using combinations of the following terms: 'spatial omics', 'fertility', 'reproduction', 'gametogenesis', 'embryogenesis', 'reproductive cancer', 'spatial transcriptomics', 'spermatogenesis', 'ovary', 'uterus', 'cervix', 'testis', and other keywords related to the subject area. All relevant publications until April 2023 were critically evaluated and discussed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Outcomes: &lt;/strong&gt;First, an overview of the ST technologies that have been applied to studying the reproductive systems was provided. The basic design principles and the advantages and limitations of these technologies were discussed and tabulated to serve as a guide for researchers to choose the best-suited technologies for their own research. Second, novel biological insights into mammalian reproduction, especially human reproduction revealed by ST analyses, were comprehensively reviewed. Three major themes were discussed. The first theme focuses on genes with non-random spatial expression patterns with specialized functions in multiple reproductive systems; The second theme centers around functionally interacting cell types which are often found to be spatially clustered in the reproductive tissues; and the thrid theme discusses pathological states in reproductive systems which are often associated with unique","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"794-810"},"PeriodicalIF":14.8,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9677176","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
PCOS during the menopausal transition and after menopause: a systematic review and meta-analysis. 绝经过渡期和绝经后多囊卵巢综合征:系统回顾和荟萃分析。
IF 14.8 1区 医学 Q1 OBSTETRICS & GYNECOLOGY
Human Reproduction Update
Pub Date : 2023-11-02 DOI: 10.1093/humupd/dmad015
Mercedes Millán-de-Meer, Manuel Luque-Ramírez, Lía Nattero-Chávez, Héctor F Escobar-Morreale
<p><strong>Background: </strong>Current knowledge about the consequences of PCOS during the late reproductive years and after menopause is limited.</p><p><strong>Objective and rationale: </strong>We performed a systematic review and meta-analysis of data on the pathophysiology, clinical manifestations, diagnosis, prognosis, and treatment of women ≥45 years of age-peri- or postmenopausal-with PCOS.</p><p><strong>Search methods: </strong>Studies published up to 15 April 2023, identified by Entrez-PubMed, EMBASE, and Scopus online facilities, were considered. We included cross-sectional or prospective studies that reported data from peri- or postmenopausal patients with PCOS and control women with a mean age ≥45 years. Three independent researchers performed data extraction. Meta-analyses of quantitative data used random-effects models because of the heterogeneity derived from differences in study design and criteria used to define PCOS, among other confounding factors. Sensitivity analyses restricted the meta-analyses to population-based studies, to studies including only patients diagnosed using the most widely accepted definitions of PCOS, only menopausal women or only women not submitted to ovarian surgery, and studies in which patients and controls presented with similar indexes of weight excess. Quality of evidence was assessed using the GRADE system.</p><p><strong>Outcomes: </strong>The initial search identified 1400 articles, and another six were included from the reference lists of included articles; 476 duplicates were deleted. We excluded 868 articles for different reasons, leaving 37 valid studies for the qualitative synthesis, of which 28 studies-published in 41 articles-were considered for the quantitative synthesis and meta-analyses. Another nine studies were included only in the qualitative analyses. Compared with controls, peri- and postmenopausal patients with PCOS presented increased circulating total testosterone (standardized mean difference, SMD 0.78 (0.35, 1.22)), free androgen index (SMD 1.29 (0.89, 1.68)), and androstenedione (SMD 0.58 (0.23, 0.94)), whereas their sex hormone-binding globulin was reduced (SMD -0.60 (-0.76, -0.44)). Women with PCOS showed increased BMI (SMD 0.57 (0.32, 0.75)), waist circumference (SMD 0.64 (0.42, 0.86)), and waist-to-hip ratio (SMD 0.38 (0.14, 0.61)) together with increased homeostasis model assessment of insulin resistance (SMD 0.56 (0.27, 0.84)), fasting insulin (SMD 0.61 (0.38, 0.83)), fasting glucose (SMD 0.48 (0.29, 0.68)), and odds ratios (OR, 95% CI) for diabetes (OR 3.01 (1.91, 4.73)) compared to controls. Women with PCOS versus controls showed decreased HDL concentrations (SMD -0.32 (-0.46, -0.19)) and increased triglycerides (SMD 0.31 (0.16, 0.46)), even though total cholesterol and LDL concentrations, as well as the OR for dyslipidaemia, were similar to those of controls. The OR for having hypertension was increased in women with PCOS compared with controls (OR 1.79 (1.36, 2.36)).
背景：目前对多囊卵巢综合征在生育后期和绝经后的后果的了解有限。目的和原理：我们对≥45岁女性的病理生理学、临床表现、诊断、预后和治疗数据进行了系统回顾和荟萃分析 年龄为围绝经期或绝经后多囊卵巢综合征患者。检索方法：截至2023年4月15日发表的研究，由Entrez PubMed、EMBASE和Scopus在线机构鉴定，被考虑在内。我们纳入了横断面或前瞻性研究，这些研究报告了围绝经期或绝经后多囊卵巢综合征患者和平均年龄≥45岁的对照女性的数据 年。三名独立研究人员进行了数据提取。定量数据的荟萃分析使用了随机效应模型，因为研究设计和用于定义多囊卵巢综合征的标准的差异以及其他混杂因素导致了异质性。敏感性分析将荟萃分析局限于基于人群的研究，仅包括使用最广泛接受的多囊卵巢综合征定义诊断的患者，仅包括更年期妇女或未接受卵巢手术的妇女，以及患者和对照组出现类似超重指标的研究。使用GRADE系统评估证据质量。结果：最初的搜索确定了1400篇文章，另外6篇从收录文章的参考文献列表中被收录；删除476个重复项。由于不同原因，我们排除了868篇文章，剩下37项有效的研究用于定性合成，其中41篇文章中发表的28项研究用于定量合成和荟萃分析。另有9项研究仅包含在定性分析中。与对照组相比，围绝经期和绝经后多囊卵巢综合征患者的循环总睾酮（标准化平均差，SMD 0.78（0.35，1.22））、游离雄激素指数（SMD 1.29（0.89，1.68））和雄烯二酮（SMD 0.58（0.23，0.94））增加，而其性激素结合球蛋白降低（SMD-0.60（-0.76，-0.44））。患有多囊卵巢综合征的女性表现出BMI（SMD 0.57（0.32，0.75））、腰围（SMD 0.64（0.42，0.86））和腰臀比（SMD 0.38（0.14，0.61））增加，同时胰岛素抵抗（SMD 0.5 6（0.27，0.84））、空腹胰岛素（SMD 0.6 1（0.38，0.83））的稳态模型评估增加，与对照组相比，空腹血糖（SMD 0.48（0.29，0.68））和糖尿病的比值比（OR，95%CI）（OR 3.01（1.91，4.73））。尽管总胆固醇和低密度脂蛋白浓度以及血脂异常的OR与对照组相似，但患有多囊卵巢综合征的女性与对照组相比，HDL浓度降低（SMD-0.32（-0.46，-0.19）），甘油三酯升高（SMD 0.31（0.16，0.46））。与对照组相比，PCOS女性患高血压的OR升高（OR 1.79（1.36，2.36））。尽管心肌梗死（OR 2.51（1.08，5.81））和中风（OR 1.75（1.03，2.99））在PCOS女性中比对照组更普遍，在患者和对照组中相似。当将荟萃分析限制在多囊卵巢综合征女性和对照组平均BMI相似的研究中时，唯一具有统计学意义的差异是前者的高密度脂蛋白胆固醇浓度降低，而在绝经后多囊卵巢综合症女性和对照者BMI相似的两项研究中，患者的血清雄激素浓度增加，这表明无论肥胖与否，高雄激素血症在绝经后仍会持续。更广泛的影响：多囊卵巢综合征患者在生殖晚期和绝经后，雄激素过度似乎持续存在。大多数心脏代谢合并症是由超重和多囊卵巢综合征频繁共存引起的，这突出了在这一人群中针对肥胖的重要性。然而，纳入的研究之间存在显著的异质性，而且这里收集的证据质量总体较低，因此无法就这个问题得出明确的结论。因此，为了对这些妇女进行适当的管理，肯定需要从有力的前瞻性研究中得出指导方针。
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引用次数: 0
Obstetric and neonatal outcomes after natural versus artificial cycle frozen embryo transfer and the role of luteal phase support: a systematic review and meta-analysis. 自然与人工周期冷冻胚胎移植后的产科和新生儿结局以及黄体期支持的作用:一项系统回顾和荟萃分析
IF 13.3 1区 医学 Q1 OBSTETRICS & GYNECOLOGY
Human Reproduction Update
Pub Date : 2023-09-05 DOI: 10.1093/humupd/dmad011
T R Zaat, E B Kostova, P Korsen, M G Showell, F Mol, M van Wely
<p><strong>Background: </strong>The number of frozen embryo transfers (FET) has increased dramatically over the past decade. Based on current evidence, there is no difference in pregnancy rates when natural cycle FET (NC-FET) is compared to artificial cycle FET (AC-FET) in subfertile women. However, NC-FET seems to be associated with lower risk of adverse obstetric and neonatal outcomes compared with AC-FET cycles. Currently, there is no consensus about whether NC-FET needs to be combined with luteal phase support (LPS) or not. The question of how to prepare the endometrium for FET has now gained even more importance and taken the dimension of safety into account as it should not simply be reduced to the basic question of effectiveness.</p><p><strong>Objective and rationale: </strong>The objective of this project was to determine whether NC-FET, with or without LPS, decreases the risk of adverse obstetric and neonatal outcomes compared with AC-FET.</p><p><strong>Search methods: </strong>A systematic review and meta-analysis was carried out. A literature search was performed using the following databases: CINAHL, EMBASE, and MEDLINE from inception to 10 October 2022. Observational studies, including cohort studies, and registries comparing obstetric and neonatal outcomes between singleton pregnancies after NC-FET and those after AC-FET were sought. Risk of bias was assessed using the ROBINS-I tool. The quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. We calculated pooled odds ratios (ORs), pooled risk differences (RDs), pooled adjusted ORs, and prevalence estimates with 95% CI using a random effect model, while heterogeneity was assessed by the I2.</p><p><strong>Outcomes: </strong>The conducted search identified 2436 studies, 890 duplicates were removed and 1546 studies were screened. Thirty studies (NC-FET n = 56 445; AC-FET n = 57 231) were included, 19 of which used LPS in NC-FET. Birthweight was lower following NC-FET versus AC-FET (mean difference 26.35 g; 95% CI 11.61-41.08, I2 = 63%). Furthermore NC-FET compared to AC-FET resulted in a lower risk of large for gestational age (OR 0.88, 95% 0.83-0.94, I2 = 54%), macrosomia (OR 0.81; 95% CI 0.71-0.93, I2 = 68%), low birthweight (OR 0.81, 95% CI 0.77-0.85, I2 = 41%), early pregnancy loss (OR 0.73; 95% CI 0.61-0.86, I2 = 70%), preterm birth (OR 0.80; 95% CI 0.75-0.85, I2 = 20%), very preterm birth (OR 0.66, 95% CI 0.53-0.84, I2 = 0%), hypertensive disorders of pregnancy (OR 0.60, 95% CI 0.50-0.65, I2 = 61%), pre-eclampsia (OR 0.50; 95% CI 0.42-0.60, I2 = 44%), placenta previa (OR 0.84, 95% CI 0.73-0.97, I2 = 0%), and postpartum hemorrhage (OR 0.43; 95% CI 0.38-0.48, I2 = 53%). Stratified analyses on LPS use in NC-FET suggested that, compared to AC-FET, NC-FET with LPS decreased preterm birth risk, while NC-FET without LPS did not (OR 0.75, 95% CI 0.70-0.81). LPS use did not modify the other outcomes. Heterogeneity varied from
背景:在过去的十年中，冷冻胚胎移植(FET)的数量急剧增加。根据目前的证据，在低生育能力妇女中，自然周期FET (NC-FET)与人工周期FET (AC-FET)相比，妊娠率没有差异。然而，与AC-FET周期相比，NC-FET似乎与较低的不良产科和新生儿结局风险相关。目前，对于NC-FET是否需要与黄体期支持(LPS)联合使用，尚未达成共识。如何为FET准备子宫内膜的问题现在变得更加重要，并考虑到安全方面，因为它不应简单地简化为有效性的基本问题。目的和理由:该项目的目的是确定与AC-FET相比，NC-FET在加或不加LPS的情况下是否降低了产科和新生儿不良结局的风险。检索方法:进行系统综述和荟萃分析。使用以下数据库进行文献检索:CINAHL、EMBASE和MEDLINE，检索时间为成立至2022年10月10日。观察性研究，包括队列研究，以及比较NC-FET和AC-FET后单胎妊娠的产科和新生儿结局的登记。使用ROBINS-I工具评估偏倚风险。采用建议分级评估、发展和评价方法评价证据质量。我们使用随机效应模型计算合并优势比(or)、合并风险差异(RDs)、合并调整后的or和95% CI的患病率估计值，同时通过I2评估异质性。结果:进行的检索确定了2436项研究，删除了890项重复，筛选了1546项研究。30项研究(NC-FET n = 56 445;共纳入AC-FET (n = 57 231)，其中19例采用LPS处理NC-FET。与AC-FET相比，NC-FET的出生体重更低(平均差26.35 g;95% ci 11.61-41.08, i2 = 63%)。此外，与AC-FET相比，NC-FET导致大胎龄(OR 0.88, 95% 0.83-0.94, I2 = 54%)、巨大儿(OR 0.81;95% CI 0.71-0.93, I2 = 68%)，低出生体重(OR 0.81, 95% CI 0.77-0.85, I2 = 41%)，早孕丢失(OR 0.73;95% CI 0.61-0.86, I2 = 70%)，早产(OR 0.80;95% CI 0.75-0.85, I2 = 20%)，重度早产(OR 0.66, 95% CI 0.53-0.84, I2 = 0%)，妊娠期高血压疾病(OR 0.60, 95% CI 0.50-0.65, I2 = 61%)，先兆子痫(OR 0.50;95% CI 0.42-0.60, I2 = 44%)、前置胎盘(OR 0.84, 95% CI 0.73-0.97, I2 = 0%)和产后出血(OR 0.43;95% ci 0.38-0.48, i2 = 53%)。对LPS在NC-FET中使用的分层分析表明，与AC-FET相比，LPS的NC-FET降低了早产风险，而不使用LPS的NC-FET则没有(OR 0.75, 95% CI 0.70-0.81)。LPS的使用没有改变其他结果。异质性从低到高，证据质量从极低到中等。更广泛的影响:本研究证实，与AC-FET相比，NC-FET降低了不良产科和新生儿结局的风险。我们估计，对于每一种不良后果，使用NC-FET可预防每1000名妇女4至22例。因此，NC-FET应该是排卵周期接受FET的女性的首选治疗方法。基于非常低质量的证据，与AC-FET相比，在NC-FET中使用LPS可降低早产风险。然而，由于存在许多不确定性，主要是关于脂多糖使用的有效性的争论，因此需要对脂多糖的有效性和安全性进行进一步的研究，目前还不能对脂多糖的使用提出建议。
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引用次数: 5
Insights from Mendelian randomization and genetic correlation analyses into the relationship between endometriosis and its comorbidities. 对子宫内膜异位症及其合并症之间关系的孟德尔随机化和遗传相关性分析的见解。
IF 16.1 1区 医学 Q1 OBSTETRICS & GYNECOLOGY
Human Reproduction Update
Pub Date : 2023-09-05 DOI: 10.1093/humupd/dmad009
Isabelle M McGrath, Grant W Montgomery, Sally Mortlock

Background: Endometriosis remains a poorly understood disease, despite its high prevalence and debilitating symptoms. The overlap in symptoms and the increased risk of multiple other traits in women with endometriosis is becoming increasingly apparent through epidemiological data. Genetic studies offer a method of investigating these comorbid relationships through the assessment of causal relationships with Mendelian randomization (MR), as well as identification of shared genetic variants and genes involved across traits. This has the capacity to identify risk factors for endometriosis as well as provide insight into the aetiology of disease.

Objective and rationale: We aim to review the current literature assessing the relationship between endometriosis and other traits using genomic data, primarily through the methods of MR and genetic correlation. We critically examine the limitations of these studies in accordance with the assumptions of the utilized methods.

Search methods: The PubMed database was used to search for peer-reviewed original research articles using the terms 'Mendelian randomization endometriosis' and '"genetic correlation" endometriosis'. Additionally, a Google Scholar search using the terms '"endometriosis" "mendelian randomization" "genetic correlation"' was performed. All relevant publications (n = 21) published up until 7 October 2022 were included in this review. Upon compilation of all traits with published MR and/or genetic correlation with endometriosis, additional epidemiological and genetic information on their comorbidity with endometriosis was sourced by searching for the trait in conjunction with 'endometriosis' on Google Scholar.

Outcomes: The association between endometriosis and multiple pain, gynaecological, cancer, inflammatory, gastrointestinal, psychological, and anthropometric traits has been assessed using MR analysis and genetic correlation analysis. Genetic correlation analyses provide evidence that genetic factors contributing to endometriosis are shared with multiple traits: migraine, uterine fibroids, subtypes of ovarian cancer, melanoma, asthma, gastro-oesophageal reflux disease, gastritis/duodenitis, and depression, suggesting the involvement of multiple biological mechanisms in endometriosis. The assessment of causality with MR has revealed several potential causes (e.g. depression) and outcomes (e.g. ovarian cancer and uterine fibroids) of a genetic predisposition to endometriosis; however, interpretation of these results requires consideration of potential violations of the MR assumptions.

Wider implications: Genomic studies have demonstrated that there is a molecular basis for the co-occurrence of endometriosis with other traits. Dissection of this overlap has identified shared genes and pathways, which provide insight into the biology of endometriosis. Thoughtful MR studies are neces

背景：尽管子宫内膜异位症的发病率很高，症状也使人衰弱，但它仍然是一种鲜为人知的疾病。流行病学数据显示，子宫内膜异位症患者的症状重叠和多种其他特征的风险增加越来越明显。遗传学研究提供了一种通过孟德尔随机化（MR）评估因果关系，以及识别共享遗传变异和跨性状相关基因来调查这些共病关系的方法。这有能力识别子宫内膜异位症的风险因素，并提供对疾病病因的见解。目的和原理：我们的目的是回顾目前使用基因组数据评估子宫内膜异位症和其他性状之间关系的文献，主要通过MR和遗传相关性的方法。我们根据所用方法的假设，严格审查了这些研究的局限性。搜索方法：PubMed数据库用于搜索同行评审的原始研究文章，使用术语“孟德尔随机化子宫内膜异位症”和“遗传相关性”子宫内膜异位病。此外，谷歌学者使用“子宫内膜异位症”、“孟德尔随机化”、“遗传相关性”进行了搜索。所有相关出版物（n = 截至2022年10月7日发布的21）包含在本综述中。在汇编了与子宫内膜异位症的已发表MR和/或遗传相关性的所有特征后，通过在Google Scholar上搜索与“子宫内膜异位”相关的特征，获得了关于其与子宫内膜内膜异位症共病的额外流行病学和遗传信息。结果：子宫内膜异位与多种疼痛、妇科、癌症、炎症、，胃肠道、心理和人体测量特征已经使用MR分析和遗传相关性分析进行了评估。遗传相关性分析表明，导致子宫内膜异位症的遗传因素具有多种特征：偏头痛、子宫肌瘤、卵巢癌症亚型、黑色素瘤、哮喘、胃食管反流病、胃炎/十二指肠炎和抑郁症，这表明子宫内膜异位病涉及多种生物学机制。对MR因果关系的评估揭示了子宫内膜异位症遗传易感性的几个潜在原因（如抑郁症）和结果（如卵巢癌症和子宫肌瘤）；然而，对这些结果的解释需要考虑潜在的违反MR假设的情况。更广泛的意义：基因组研究表明，子宫内膜异位症与其他特征共同发生是有分子基础的。对这种重叠的解剖已经确定了共享的基因和途径，这为子宫内膜异位症的生物学提供了见解。为了确定子宫内膜异位症合并症的因果关系，有必要进行深思熟虑的MR研究。考虑到7-11岁子宫内膜异位症的诊断延迟 多年来，确定危险因素对于帮助诊断和减轻疾病负担是必要的。识别子宫内膜异位症是一个危险因素的特征对于患者的整体治疗和咨询很重要。利用基因组数据来理清子宫内膜异位症与其他特征的重叠，为子宫内膜异位的病因提供了见解。
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