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Planned oocyte cryopreservation: a systematic review and meta-regression analysis 计划性卵母细胞冷冻:系统综述和元回归分析
IF 13.3 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-04-24 DOI: 10.1093/humupd/dmae009
Ayala Hirsch, Bruria Hirsh Raccah, Reut Rotem, Jordana H Hyman, Ido Ben-Ami, Avi Tsafrir
BACKGROUND Awareness of the age-related decline in fertility potential has increased the popularity of planned oocyte cryopreservation (POC). However, data regarding outcomes of POC, including rates of women returning to thaw oocytes, as well as pregnancy and live birth rates, are scarce and based mostly on small case series. OBJECTIVE AND RATIONALE POC was defined as cryopreservation exclusively for prevention of future age-related fertility loss. The primary outcome was live birth rate per patient. The secondary outcomes included the return to thaw rate and laboratory outcomes. A meta-regression analysis examining the association between live birth and age above 40 or below 35 was conducted. SEARCH METHODS We conducted a systematic database search from inception to August 2022. The search included PubMed (MEDLINE) and EMBASE. Our search strategies employed a combination of index terms (Mesh) and free text words to compile relevant concepts. The systematic review and meta-regression were undertaken following registration of systematic review (PROSPERO registration number CRD42022361791) and were reported following guidelines of Preferred Reporting Items for Systematic Review and Meta-Analyses 2020 (PRISMA 2020). OUTCOMES The database search yielded 3847 records. After the selection process, 10 studies, conducted from 1999 to 2020, were included. Overall, 8750 women underwent POC, with a mean cryopreservation age of 37.2 (±0.8). Of those, 1517 women returned to use their oocytes with a return rate of 11.1% (± 4.7%). The mean age at the time of cryopreservation for women who returned to use their oocytes was 38.1 (±0.4), with an average of 12.6 (±3.6) cryopreserved oocytes per woman. In a meta-analysis, the oocyte survival rate was 78.5% with a 95% CI of 0.74–0.83 (I2 = 93%). The live birth rate per patient was 28% with a 95% CI of 0.24–0.33 (I2 = 92%). Overall, 447 live births were reported. In a sub-group analysis, women who underwent cryopreservation at age ≥40 achieved a live birth rate per patient of 19% (95% CI 0.13–0.29, I2 = 6%), while women aged ≤35 years old or younger had a higher live birth rate per patient of 52% (95% CI 0.41–0.63, I2 = 7%). WIDER IMPLICATIONS POC emerges as a feasible option for women aiming to improve their chances of conceiving at a later reproductive age. Nonetheless, it must be acknowledged that the overall success rates of POC are limited and that the likelihood of successful live birth declines as the age at cryopreservation rises. With increasing interest in POC, the collation of comprehensive and high-quality data is imperative to clearly define the outcomes for various age groups. REGISTRATION NUMBER CRD42022361791.
背景:随着年龄的增长,人们逐渐意识到生育能力的下降,因此有计划地进行卵母细胞冷冻保存(POC)越来越受欢迎。然而,有关 POC 的结果(包括妇女返回解冻卵母细胞的比率以及怀孕率和活产率)的数据却很少,而且大多基于小型病例系列。目标和原理 POC 被定义为专门为预防未来与年龄相关的生育能力丧失而进行的冷冻保存。主要结果是每位患者的活产率。次要结果包括解冻恢复率和实验室结果。对活产率与 40 岁以上或 35 岁以下年龄之间的关系进行了元回归分析。检索方法 我们进行了从开始到 2022 年 8 月的系统性数据库检索。检索包括 PubMed (MEDLINE) 和 EMBASE。我们的检索策略采用了索引词(Mesh)和自由文本词相结合的方式来汇编相关概念。系统综述和荟萃回归是在系统综述注册(PROSPERO 注册号为 CRD42022361791)后进行的,并按照《2020 年系统综述和荟萃分析首选报告项目》(PRISMA 2020)指南进行报告。结果 数据库搜索共获得 3847 条记录。经过筛选,共纳入了 10 项研究,这些研究是在 1999 年至 2020 年期间进行的。共有 8750 名女性接受了 POC,平均冷冻年龄为 37.2 (±0.8)岁。其中,1517 名妇女返回使用了她们的卵母细胞,返回率为 11.1%(± 4.7%)。返回使用卵母细胞的妇女冷冻保存时的平均年龄为 38.1(±0.4)岁,平均每位妇女冷冻保存 12.6(±3.6)个卵母细胞。在一项荟萃分析中,卵母细胞存活率为 78.5%,95% CI 为 0.74-0.83(I2 = 93%)。每位患者的活产率为 28%,95% CI 为 0.24-0.33 (I2 = 92%)。总计报告了 447 例活产。在一项亚组分析中,年龄≥40 岁时接受冷冻保存的女性每例活产率为 19% (95% CI 0.13-0.29, I2 = 6%),而年龄≤35 岁或更小的女性每例活产率更高,为 52% (95% CI 0.41-0.63, I2 = 7%)。更广泛的启示 对于希望提高晚育几率的女性来说,POC 是一个可行的选择。然而,必须承认的是,POC 的总体成功率是有限的,而且随着冷冻年龄的增加,成功活产的可能性也在下降。随着人们对 POC 的兴趣与日俱增,当务之急是整理全面、高质量的数据,以明确界定不同年龄组的结果。注册号:CRD42022361791。
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引用次数: 0
Reply: Endometrial scratching: the light at the end of the tunnel. 回复:子宫内膜搔痒:隧道尽头的曙光。
IF 13.3 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-03-01 DOI: 10.1093/humupd/dmad038
N E van Hoogenhuijze, F J M Broekmans
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引用次数: 0
COVID-19 in pregnant women: a systematic review and meta-analysis on the risk and prevalence of pregnancy loss. 孕妇中的COVID-19:关于妊娠丢失风险和流行率的系统回顾和荟萃分析
IF 14.8 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-03-01 DOI: 10.1093/humupd/dmad030
Janneke A C van Baar, Elena B Kostova, John Allotey, Shakila Thangaratinam, Javier R Zamora, Mercedes Bonet, Caron Rahn Kim, Lynne M Mofenson, Heinke Kunst, Asma Khalil, Elisabeth van Leeuwen, Julia Keijzer, Marije Strikwerda, Bethany Clark, Maxime Verschuuren, Arri Coomarasamy, Mariëtte Goddijn, Madelon van Wely
<p><strong>Background: </strong>Pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more likely to experience preterm birth and their neonates are more likely to be stillborn or admitted to a neonatal unit. The World Health Organization declared in May 2023 an end to the coronavirus disease 2019 (COVID-19) pandemic as a global health emergency. However, pregnant women are still becoming infected with SARS-CoV-2 and there is limited information available regarding the effect of SARS-CoV-2 infection in early pregnancy on pregnancy outcomes.</p><p><strong>Objective and rationale: </strong>We conducted this systematic review to determine the prevalence of early pregnancy loss in women with SARS-Cov-2 infection and compare the risk to pregnant women without SARS-CoV-2 infection.</p><p><strong>Search methods: </strong>Our systematic review is based on a prospectively registered protocol. The search of PregCov19 consortium was supplemented with an extra electronic search specifically on pregnancy loss in pregnant women infected with SARS-CoV-2 up to 10 March 2023 in PubMed, Google Scholar, and LitCovid. We included retrospective and prospective studies of pregnant women with SARS-CoV-2 infection, provided that they contained information on pregnancy losses in the first and/or second trimester. Primary outcome was miscarriage defined as a pregnancy loss before 20 weeks of gestation, however, studies that reported loss up to 22 or 24 weeks were also included. Additionally, we report on studies that defined the pregnancy loss to occur at the first and/or second trimester of pregnancy without specifying gestational age, and for second trimester miscarriage only when the study presented stillbirths and/or foetal losses separately from miscarriages. Data were stratified into first and second trimester. Secondary outcomes were ectopic pregnancy (any extra-uterine pregnancy), and termination of pregnancy. At least three researchers independently extracted the data and assessed study quality. We calculated odds ratios (OR) and risk differences (RDs) with corresponding 95% CI and pooled the data using random effects meta-analysis. To estimate risk prevalence, we performed meta-analysis on proportions. Heterogeneity was assessed by I2.</p><p><strong>Outcomes: </strong>We included 120 studies comprising a total of 168 444 pregnant women with SARS-CoV-2 infection; of which 18 233 women were in their first or second trimester of pregnancy. Evidence level was considered to be of low to moderate certainty, mostly owing to selection bias. We did not find evidence of an association between SARS-CoV-2 infection and miscarriage (OR 1.10, 95% CI 0.81-1.48; I2 = 0.0%; RD 0.0012, 95% CI -0.0103 to 0.0127; I2 = 0%; 9 studies, 4439 women). Miscarriage occurred in 9.9% (95% CI 6.2-14.0%; I2 = 68%; 46 studies, 1797 women) of the women with SARS CoV-2 infection in their first trimester and in 1.2% (95% CI 0.3-2.4%; I2 = 34%; 33 studies; 31
背景:感染了严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)的孕妇更容易出现早产,其新生儿更容易死产或住进新生儿病房。世界卫生组织于2023年5月宣布2019冠状病毒病(COVID-19)大流行结束,这是全球卫生紧急情况。然而,孕妇仍然会感染SARS-CoV-2,并且关于妊娠早期感染SARS-CoV-2对妊娠结局的影响的信息有限。目的和理由:我们进行了本系统综述,以确定感染SARS-Cov-2的妇女早期妊娠流产的发生率,并将其与未感染SARS-Cov-2的孕妇的风险进行比较。检索方法:我们的系统综述基于前瞻性注册方案。在PubMed、Google Scholar和LitCovid中对PregCov19联合体的搜索进行了额外的电子搜索,专门针对截至2023年3月10日感染SARS-CoV-2的孕妇的妊娠损失进行了搜索。我们纳入了SARS-CoV-2感染孕妇的回顾性和前瞻性研究,前提是这些研究包含妊娠早期和/或中期妊娠损失的信息。主要结局是流产,定义为妊娠20周前的流产,然而,报告妊娠22或24周流产的研究也包括在内。此外,我们还报道了一些研究,这些研究将妊娠丢失定义为发生在妊娠的第一个和/或第二个三个月,而没有指定胎龄,并且只有当研究将死产和/或胎儿丢失与流产分开时,才会将妊娠丢失定义为第二个三个月流产。数据分为妊娠早期和中期。次要结局是异位妊娠(任何子宫外妊娠)和终止妊娠。至少有三名研究人员独立提取数据并评估研究质量。我们以相应的95% CI计算优势比(OR)和风险差异(RDs),并使用随机效应荟萃分析汇总数据。为了估计风险患病率,我们对比例进行了荟萃分析。异质性采用I2评估。结果:我们纳入了120项研究,共包括164844名感染SARS-CoV-2的孕妇;其中18233名妇女处于妊娠早期或中期。证据水平被认为是低到中等确定性,主要是由于选择偏差。我们没有发现SARS-CoV-2感染与流产之间存在关联的证据(OR 1.10, 95% CI 0.81-1.48;I2 = 0.0%;RD为0.0012,95% CI为-0.0103 ~ 0.0127;I2 = 0%;9项研究,4439名女性)。流产发生率为9.9% (95% CI 6.2-14.0%;I2 = 68%;46项研究,1797名妇女)在妊娠早期感染SARS - CoV-2的妇女和1.2% (95% CI 0.3-2.4%;i2 = 34%;33个研究;3159名妇女)在妊娠中期。SARS-CoV-2感染妇女宫外孕的比例为1.4% (95% CI 0.02-4.2%;i2 = 66%;14项研究,950名女性)。终止妊娠发生率为0.6% (95% CI 0.01-1.6%;i2 = 79%;39岁的研究;1166名女性)。更广泛的影响:我们的研究发现,没有迹象表明在妊娠早期或中期感染SARS-CoV-2会增加流产的风险。为了提供更好的风险估计,需要设计良好的研究,包括怀孕和妊娠早期感染SARS-CoV-2和未感染SARS-CoV-2的孕妇,并考虑SARS-CoV-2感染的临床表现和严重程度与妊娠丢失的关系,以及潜在的混杂因素,如既往妊娠丢失。在临床实践中,仍应建议孕妇采取预防措施,避免暴露于SARS-CoV-2的风险,并接种SARS-CoV-2疫苗。
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引用次数: 0
Declining global fertility rates and the implications for family planning and family building: an IFFS consensus document based on a narrative review of the literature. 全球生育率下降及其对计划生育和家庭建设的影响:根据对文献的叙述性审查编写的森林论坛共识文件。
IF 14.8 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-03-01 DOI: 10.1093/humupd/dmad028
Bart C J M Fauser, G David Adamson, Jacky Boivin, Georgina M Chambers, Christian de Geyter, Silke Dyer, Marcia C Inhorn, Lone Schmidt, Gamal I Serour, Basil Tarlatzis, Fernando Zegers-Hochschild
<p><strong>Background: </strong>Family-planning policies have focused on contraceptive approaches to avoid unintended pregnancies, postpone, or terminate pregnancies and mitigate population growth. These policies have contributed to significantly slowing world population growth. Presently, half the countries worldwide exhibit a fertility rate below replacement level. Not including the effects of migration, many countries are predicted to have a population decline of >50% from 2017 to 2100, causing demographic changes with profound societal implications. Policies that optimize chances to have a child when desired increase fertility rates and are gaining interest as a family-building method. Increasingly, countries have implemented child-friendly policies (mainly financial incentives in addition to public funding of fertility treatment in a limited number of countries) to mitigate decreasing national populations. However, the extent of public spending on child benefits varies greatly from country to country. To our knowledge, this International Federation of Fertility Societies (IFFS) consensus document represents the first attempt to describe major disparities in access to fertility care in the context of the global trend of decreasing growth in the world population, based on a narrative review of the existing literature.</p><p><strong>Objective and rationale: </strong>The concept of family building, the process by which individuals or couples create or expand their families, has been largely ignored in family-planning paradigms. Family building encompasses various methods and options for individuals or couples who wish to have children. It can involve biological means, such as natural conception, as well as ART, surrogacy, adoption, and foster care. Family-building acknowledges the diverse ways in which individuals or couples can create their desired family and reflects the understanding that there is no one-size-fits-all approach to building a family. Developing education programs for young adults to increase family-building awareness and prevent infertility is urgently needed. Recommendations are provided and important knowledge gaps identified to provide professionals, the public, and policymakers with a comprehensive understanding of the role of child-friendly policies.</p><p><strong>Search methods: </strong>A narrative review of the existing literature was performed by invited global leaders who themselves significantly contributed to this research field. Each section of the review was prepared by two to three experts, each of whom searched the published literature (PubMed) for peer reviewed full papers and reviews. Sections were discussed monthly by all authors and quarterly by the review board. The final document was prepared following discussions among all team members during a hybrid invitational meeting where full consensus was reached.</p><p><strong>Outcomes: </strong>Major advances in fertility care have dramatically improved family-b
背景:计划生育政策侧重于避孕方法,以避免意外怀孕、推迟或终止妊娠以及减缓人口增长。这些政策大大减缓了世界人口的增长。目前,全世界有一半国家的生育率低于更替水平。如果不考虑移民的影响,预计从 2017 年到 2100 年,许多国家的人口将下降 50%以上,这将导致对社会产生深远影响的人口变化。优化生育机会的政策会提高生育率,并作为一种家庭建设方法受到越来越多的关注。越来越多的国家实施了有利于儿童的政策(主要是财政激励措施,少数国家还为生育治疗提供公共资金),以缓解国家人口减少的问题。然而,各国在儿童福利方面的公共开支差异很大。据我们所知,这份国际生育协会联合会(IFFS)共识文件是在对现有文献进行叙述性回顾的基础上,首次尝试描述在世界人口增长下降的全球趋势下,在获得生育保健方面存在的主要差异。目标和理由:家庭建设的概念是个人或夫妇创建或扩大家庭的过程,在计划生育范例中基本上被忽视了。家庭建设包括希望生育子女的个人或夫妇的各种方法和选择。它既包括自然受孕等生物学手段,也包括 ART、代孕、领养和寄养。家庭建设承认个人或夫妇可以通过不同的方式建立自己想要的家庭,并反映了这样一种认识,即建立家庭没有放之四海而皆准的方法。当务之急是为年轻人制定教育计划,以提高建立家庭的意识并预防不孕不育。本文提出了一些建议,并指出了重要的知识缺口,以便让专业人士、公众和政策制定者全面了解爱幼政策的作用:检索方法:邀请对该研究领域做出重大贡献的全球领导者对现有文献进行了叙述性综述。综述的每个部分都由两到三位专家准备,每位专家都在已发表的文献(PubMed)中搜索同行评审的完整论文和综述。所有作者每月讨论一次,评审委员会每季度讨论一次。在一次混合邀请会议上,所有小组成员进行了讨论,并达成了完全一致的意见,随后编写了最终文件:自 20 世纪 90 年代以来,生育护理方面的重大进步极大地改善了建立家庭的机会。尽管在一些富裕国家,有高达 10%的儿童是通过生育护理出生的,但在获得护理方面却存在很大差异。不孕不育治疗的高昂费用使大多数患者负担不起。初步研究表明,生育保健对全球人口的贡献越来越大,并为社会带来了相关的经济效益:生育保健很少在世界人口增长迅速下降的背景下进行讨论。很快,大多数国家每名妇女的平均子女数将远远低于更替水平。虽然这可能会对环境产生有利影响,但许多国家都非常担心人口不足的问题。尽管各国政府已经实施了关爱儿童的政策,但在获得生育护理方面仍存在明显差异。
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引用次数: 0
IVF versus IUI with ovarian stimulation for unexplained infertility: a collaborative individual participant data meta-analysis. 试管婴儿与人工授精加卵巢刺激治疗不明原因不孕症:个人参与者数据合作荟萃分析。
IF 14.8 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-03-01 DOI: 10.1093/humupd/dmad033
Shimona Lai, Rui Wang, Madelon van Wely, Michael Costello, Cindy Farquhar, Alexandra J Bensdorp, Inge M Custers, Angelique J Goverde, Hossam Elzeiny, Ben W Mol, Wentao Li
<p><strong>Background: </strong>IVF and IUI with ovarian stimulation (IUI-OS) are widely used in managing unexplained infertility. IUI-OS is generally considered first-line therapy, followed by IVF only if IUI-OS is unsuccessful after several attempts. However, there is a growing interest in using IVF for immediate treatment because it is believed to lead to higher live birth rates and shorter time to pregnancy.</p><p><strong>Objective and rationale: </strong>Randomized controlled trials (RCTs) comparing IVF versus IUI-OS had varied study designs and findings. Some RCTs used complex algorithms to combine IVF and IUI-OS, while others had unequal follow-up time between arms or compared treatments on a per-cycle basis, which introduced biases. Comparing cumulative live birth rates of IVF and IUI-OS within a consistent time frame is necessary for a fair head-to-head comparison. Previous meta-analyses of RCTs did not consider the time it takes to achieve pregnancy, which is not possible using aggregate data. Individual participant data meta-analysis (IPD-MA) allows standardization of follow-up time in different trials and time-to-event analysis methods. We performed this IPD-MA to investigate if IVF increases cumulative live birth rate considering the time leading to pregnancy and reduces multiple pregnancy rate compared to IUI-OS in couples with unexplained infertility.</p><p><strong>Search methods: </strong>We searched MEDLINE, EMBASE, CENTRAL, PsycINFO, CINAHL, and the Cochrane Gynaecology and Fertility Group Specialised Register to identify RCTs that completed data collection before June 2021. A search update was carried out in January 2023. RCTs that compared IVF/ICSI to IUI-OS in couples with unexplained infertility were eligible. We invited author groups of eligible studies to join the IPD-MA and share the deidentified IPD of their RCTs. IPD were checked and standardized before synthesis. The quality of evidence was assessed using the Risk of Bias 2 tool.</p><p><strong>Outcomes: </strong>Of eight potentially eligible RCTs, two were considered awaiting classification. In the other six trials, four shared IPD of 934 women, of which 550 were allocated to IVF and 383 to IUI-OS. Because the interventions were unable to blind, two RCTs had a high risk of bias, one had some concerns, and one had a low risk of bias. Considering the time to pregnancy leading to live birth, the cumulative live birth rate was not significantly higher in IVF compared to that in IUI-OS (4 RCTs, 908 women, 50.3% versus 43.2%, hazard ratio 1.19, 95% CI 0.81-1.74, I2 = 42.4%). For the safety primary outcome, the rate of multiple pregnancy was not significantly lower in IVF than IUI-OS (3 RCTs, 890 women, 3.8% versus 5.2% of all couples randomized, odds ratio 0.78, 95% CI 0.41-1.50, I2 = 0.0%).</p><p><strong>Wider implications: </strong>There is no robust evidence that in couples with unexplained infertility IVF achieves pregnancy leading to live birth faster than IUI-OS. IVF a
背景:试管婴儿和卵巢刺激人工授精(IUI-OS)被广泛用于治疗不明原因的不孕症。人工授精-促排卵通常被认为是一线疗法,只有在人工授精-促排卵多次尝试后仍不成功的情况下,才会进行试管婴儿。然而,人们对使用体外受精进行即时治疗的兴趣日益浓厚,因为人们认为体外受精可提高活产率,缩短怀孕时间:比较体外受精与人工授精的随机对照试验(RCT)的研究设计和结果各不相同。一些随机对照试验采用复杂的算法将体外受精和人工授精-体外人工授精结合起来,而另一些试验则在两组之间采用不等的随访时间或按周期比较治疗方法,从而产生了偏差。在一致的时间框架内比较试管婴儿和人工授精-体外射精的累积活产率,是进行公平的正面比较的必要条件。以往的研究性试验荟萃分析没有考虑怀孕所需的时间,而使用综合数据则无法做到这一点。个体参与者数据荟萃分析(IPD-MA)可以对不同试验的随访时间和时间到事件分析方法进行标准化。我们进行了这项IPD-MA分析,以研究与IUI-OS相比,试管婴儿是否能在考虑到怀孕时间的情况下提高累积活产率,并降低不明原因不孕夫妇的多胎妊娠率:我们检索了 MEDLINE、EMBASE、CENTRAL、PsycINFO、CINAHL 和 Cochrane 妇科与不孕不育组专门登记册,以确定在 2021 年 6 月之前完成数据收集的 RCT。2023 年 1 月进行了一次检索更新。对不明原因不孕夫妇进行IVF/ICSI与IUI-OS比较的研究符合条件。我们邀请符合条件的研究的作者小组加入 IPD-MA,并分享其 RCT 的去标识 IPD。在综合之前,我们对IPD进行了检查和标准化。证据质量采用 "偏倚风险2 "工具进行评估:在八项可能符合条件的 RCT 中,有两项正在等待分类。在其他六项试验中,四项试验共享了934名妇女的IPD,其中550名妇女被分配到体外受精,383名妇女被分配到人工授精-体外受精。由于干预措施无法进行盲法试验,因此两项研究试验的偏倚风险较高,一项存在一些问题,一项偏倚风险较低。从怀孕到活产的时间来看,试管婴儿的累积活产率并没有明显高于人工授精-体外受精(4 项研究,908 名妇女,50.3% 对 43.2%,危险比 1.19,95% CI 0.81-1.74,I2 = 42.4%)。在安全性的主要结果方面,IVF的多胎妊娠率并不明显低于IUI-OS(3项研究,890名妇女,随机对照的所有夫妇中,3.8%对5.2%,几率比0.78,95% CI 0.41-1.50,I2 = 0.0%):没有确凿证据表明,对于原因不明的不孕症夫妇,试管婴儿比人工授精-体外射精更快实现妊娠,并导致活产。就治疗不明原因不孕症的有效性和安全性而言,体外受精和人工授精-体外射精都是可行的选择。在临床决策中,需要权衡干预措施的相关成本和夫妇的偏好。
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引用次数: 0
Roles of bone morphogenetic proteins in endometrial remodeling during the human menstrual cycle and pregnancy. 骨形态发生蛋白在人类月经周期和妊娠期间子宫内膜重塑中的作用。
IF 14.8 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-03-01 DOI: 10.1093/humupd/dmad031
Daimin Wei, Yaxin Su, Peter C K Leung, Yan Li, Zi-Jiang Chen
<p><strong>Background: </strong>During the human menstrual cycle and pregnancy, the endometrium undergoes a series of dynamic remodeling processes to adapt to physiological changes. Insufficient endometrial remodeling, characterized by inadequate endometrial proliferation, decidualization and spiral artery remodeling, is associated with infertility, endometriosis, dysfunctional uterine bleeding, and pregnancy-related complications such as preeclampsia and miscarriage. Bone morphogenetic proteins (BMPs), a subset of the transforming growth factor-β (TGF-β) superfamily, are multifunctional cytokines that regulate diverse cellular activities, such as differentiation, proliferation, apoptosis, and extracellular matrix synthesis, are now understood as integral to multiple reproductive processes in women. Investigations using human biological samples have shown that BMPs are essential for regulating human endometrial remodeling processes, including endometrial proliferation and decidualization.</p><p><strong>Objective and rationale: </strong>This review summarizes our current knowledge on the known pathophysiological roles of BMPs and their underlying molecular mechanisms in regulating human endometrial proliferation and decidualization, with the goal of promoting the development of innovative strategies for diagnosing, treating and preventing infertility and adverse pregnancy complications associated with dysregulated human endometrial remodeling.</p><p><strong>Search methods: </strong>A literature search for original articles published up to June 2023 was conducted in the PubMed, MEDLINE, and Google Scholar databases, identifying studies on the roles of BMPs in endometrial remodeling during the human menstrual cycle and pregnancy. Articles identified were restricted to English language full-text papers.</p><p><strong>Outcomes: </strong>BMP ligands and receptors and their transduction molecules are expressed in the endometrium and at the maternal-fetal interface. Along with emerging technologies such as tissue microarrays, 3D organoid cultures and advanced single-cell transcriptomics, and given the clinical availability of recombinant human proteins and ongoing pharmaceutical development, it is now clear that BMPs exert multiple roles in regulating human endometrial remodeling and that these biomolecules (and their receptors) can be targeted for diagnostic and therapeutic purposes. Moreover, dysregulation of these ligands, their receptors, or signaling determinants can impact endometrial remodeling, contributing to infertility or pregnancy-related complications (e.g. preeclampsia and miscarriage).</p><p><strong>Wider implications: </strong>Although further clinical trials are needed, recent advancements in the development of recombinant BMP ligands, synthetic BMP inhibitors, receptor antagonists, BMP ligand sequestration tools, and gene therapies have underscored the BMPs as candidate diagnostic biomarkers and positioned the BMP signaling pathway as a
背景:在人类月经周期和妊娠期间,子宫内膜经历了一系列动态重塑过程,以适应生理变化。子宫内膜重构不足,其特征为子宫内膜增殖不足、脱胞化和螺旋动脉重构,与不孕症、子宫内膜异位症、功能失调性子宫出血和妊娠相关并发症如先兆子痫和流产有关。骨形态发生蛋白(BMPs)是转化生长因子-β (TGF-β)超家族的一个子集,是调节多种细胞活动的多功能细胞因子,如分化、增殖、凋亡和细胞外基质合成,现在被认为是女性多种生殖过程中不可或缺的一部分。使用人类生物样本的研究表明,bmp对于调节人类子宫内膜重塑过程至关重要,包括子宫内膜增殖和去个体化。目的和理由:本文综述了目前已知的bmp在调节人子宫内膜增殖和脱个体化中的病理生理作用及其潜在的分子机制,旨在促进诊断、治疗和预防与人子宫内膜重构失调相关的不孕症和不良妊娠并发症的创新策略的发展。检索方法:检索PubMed、MEDLINE和Google Scholar数据库中截至2023年6月发表的原创文章,确定bmp在人类月经周期和妊娠期间子宫内膜重塑中的作用。确定的文章仅限于英文全文论文。结果:BMP配体和受体及其转导分子在子宫内膜和母胎界面表达。随着组织微阵列、3D类器官培养和先进的单细胞转录组学等新兴技术的发展,以及重组人类蛋白质的临床可用性和正在进行的药物开发,现在很清楚,bmp在调节人类子宫内膜重塑中发挥多种作用,这些生物分子(及其受体)可以用于诊断和治疗目的。此外,这些配体、受体或信号决定因素的失调会影响子宫内膜重塑,导致不孕或妊娠相关并发症(如先兆子痫和流产)。更广泛的意义:虽然需要进一步的临床试验,但最近在重组BMP配体、合成BMP抑制剂、受体拮抗剂、BMP配体分离工具和基因治疗方面的进展强调了BMP作为候选诊断生物标志物,并将BMP信号通路定位为解决与人类子宫内膜重构失调相关的不孕症和妊娠并发症的有希望的治疗靶点。
{"title":"Roles of bone morphogenetic proteins in endometrial remodeling during the human menstrual cycle and pregnancy.","authors":"Daimin Wei, Yaxin Su, Peter C K Leung, Yan Li, Zi-Jiang Chen","doi":"10.1093/humupd/dmad031","DOIUrl":"10.1093/humupd/dmad031","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;During the human menstrual cycle and pregnancy, the endometrium undergoes a series of dynamic remodeling processes to adapt to physiological changes. Insufficient endometrial remodeling, characterized by inadequate endometrial proliferation, decidualization and spiral artery remodeling, is associated with infertility, endometriosis, dysfunctional uterine bleeding, and pregnancy-related complications such as preeclampsia and miscarriage. Bone morphogenetic proteins (BMPs), a subset of the transforming growth factor-β (TGF-β) superfamily, are multifunctional cytokines that regulate diverse cellular activities, such as differentiation, proliferation, apoptosis, and extracellular matrix synthesis, are now understood as integral to multiple reproductive processes in women. Investigations using human biological samples have shown that BMPs are essential for regulating human endometrial remodeling processes, including endometrial proliferation and decidualization.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective and rationale: &lt;/strong&gt;This review summarizes our current knowledge on the known pathophysiological roles of BMPs and their underlying molecular mechanisms in regulating human endometrial proliferation and decidualization, with the goal of promoting the development of innovative strategies for diagnosing, treating and preventing infertility and adverse pregnancy complications associated with dysregulated human endometrial remodeling.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Search methods: &lt;/strong&gt;A literature search for original articles published up to June 2023 was conducted in the PubMed, MEDLINE, and Google Scholar databases, identifying studies on the roles of BMPs in endometrial remodeling during the human menstrual cycle and pregnancy. Articles identified were restricted to English language full-text papers.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Outcomes: &lt;/strong&gt;BMP ligands and receptors and their transduction molecules are expressed in the endometrium and at the maternal-fetal interface. Along with emerging technologies such as tissue microarrays, 3D organoid cultures and advanced single-cell transcriptomics, and given the clinical availability of recombinant human proteins and ongoing pharmaceutical development, it is now clear that BMPs exert multiple roles in regulating human endometrial remodeling and that these biomolecules (and their receptors) can be targeted for diagnostic and therapeutic purposes. Moreover, dysregulation of these ligands, their receptors, or signaling determinants can impact endometrial remodeling, contributing to infertility or pregnancy-related complications (e.g. preeclampsia and miscarriage).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Wider implications: &lt;/strong&gt;Although further clinical trials are needed, recent advancements in the development of recombinant BMP ligands, synthetic BMP inhibitors, receptor antagonists, BMP ligand sequestration tools, and gene therapies have underscored the BMPs as candidate diagnostic biomarkers and positioned the BMP signaling pathway as a","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"215-237"},"PeriodicalIF":14.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138464535","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
Endometrial scratching: the light at the end of the tunnel. 子宫内膜搔痒:隧道尽头的曙光
IF 14.8 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-03-01 DOI: 10.1093/humupd/dmad037
Amerigo Vitagliano, Ettore Cicinelli, Antonio Simone Laganà, Alessandro Favilli, Salvatore Giovanni Vitale, Marco Noventa, Gianluca Raffaello Damiani, Miriam Dellino, Pierpaolo Nicolì, Antonio D'Amato, Stefano Bettocchi, Maria Matteo, Stefano Palomba
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引用次数: 0
The complicated ART of finding consensus on family-building health policy: a comment on the IFFS consensus document. 就家庭建设健康政策达成共识的复杂艺术:对国际家庭健康论坛共识文件的评论。
IF 14.8 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-03-01 DOI: 10.1093/humupd/dmad036
Alexander Weinreb, Artur Ludwin, Hagai Levine
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引用次数: 0
A systematic review to determine use of the Endometriosis Health Profiles to measure quality of life outcomes in women with endometriosis. 子宫内膜异位症健康概况评估子宫内膜异位症患者生活质量的系统评价
IF 14.8 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-03-01 DOI: 10.1093/humupd/dmad029
Georgina L Jones, Kirsty Budds, Francesca Taylor, Danielle Musson, Justin Raymer, David Churchman, Stephen H Kennedy, Crispin Jenkinson
<p><strong>Background: </strong>The Endometriosis Health Profiles (EHPs), the EHP-30 and EHP-5, are patient-reported outcome measures that were developed to measure the health-related quality of life (HRQoL) of women living with endometriosis. Prior to their development, a systematic review was undertaken which identified that the HRQoL of women living with endometriosis was poorly understood, with only three medical and one surgical study identified.</p><p><strong>Objective and rationale: </strong>The 20-year anniversary of the EHP-30 provided a timely opportunity to assess how the tools have been used and explore what the findings tell us about the impact of endometriosis and its associated treatments upon women's QoL. Applying robust systematic review methodology, following PRISMA guidelines, we sought to answer: How many studies have used the EHP and for what purpose?; What are the demographic characteristics and international context of the studies?; What is the methodological nature and quality of the studies?; Which interventions have been assessed and what are the reported EHP outcomes?; and Can the EHP outcomes of these interventions be analysed using a meta-analysis and, if so, what do the results show?</p><p><strong>Search methods: </strong>The electronic databases MEDLINE, CINAHL, PsycINFO, PubMed, and Google Scholar were searched from the year the EHP was first published, in 2001 to 26 February 2020 using the search terms 'EHP30', 'EHP5', 'EHP-30', 'EHP-5', 'endometriosis health profile 30', and 'endometriosis health profile 5'. We updated the searches on 9 April 2021. All included studies were quality assessed using the Mixed Methods Appraisal Tool (MMAT).</p><p><strong>Outcomes: </strong>The review included 139 papers. In clinical intervention studies, the EHPs were deployed most frequently to measure the outcomes of medical (n = 35) and surgical (n = 21) treatment. The EHPs were also used in 13 other intervention studies, 29 non-interventional studies, 32 psychometric/cross cultural validation studies; six diagnostic studies, and in three other studies to measure outcomes in related conditions. They were mainly deployed in studies undertaken in Europe and North America. Overall, regardless of the nature of the intervention, most women reported improvements in HRQoL after treatment. Surgical interventions generally resulted in significant improvements for the longest amount of time. There was also evidence that when participants stopped taking medication their EHP scores worsened, perhaps reinforcing the temporary impact of medical treatment. Younger patients reported more negative impact upon their HRQoL. Further evidence using classical test theory to support the EHPs' robust psychometric properties, including acceptability, dimensionality, reliability, validity (including cross-cultural), and responsiveness, was demonstrated, particularly for the EHP-30. Strikingly, using anchor-based methods, EHP-30 responsiveness studies demon
背景:子宫内膜异位症健康概况(EHPs), EHP-30和EHP-5是患者报告的结局指标,用于测量子宫内膜异位症患者的健康相关生活质量(HRQoL)。在其发展之前,进行了一项系统审查,发现对子宫内膜异位症妇女的HRQoL了解甚少,仅确定了三项医学研究和一项外科研究。目的和理由:EHP-30 20周年提供了一个及时的机会来评估这些工具的使用情况,并探讨这些发现告诉我们子宫内膜异位症及其相关治疗对女性生活质量的影响。采用稳健的系统评价方法,遵循PRISMA指南,我们试图回答:有多少研究使用了EHP,目的是什么?这些研究的人口特征和国际背景是什么?这些研究的方法学性质和质量如何?评估了哪些干预措施,报告的EHP结果是什么?能否使用荟萃分析分析这些干预措施的EHP结果,如果可以,结果显示了什么?检索方法:检索电子数据库MEDLINE、CINAHL、PsycINFO、PubMed和Google Scholar,检索词为“EHP30”、“EHP5”、“EHP-30”、“EHP-5”、“子宫内膜异位症健康概况30”和“子宫内膜异位症健康概况5”,检索自EHP首次发表的2001年至2020年2月26日。我们于2021年4月9日更新了搜索结果。所有纳入的研究均采用混合方法评估工具(MMAT)进行质量评估。结果:本综述纳入139篇论文。在临床干预研究中,EHPs最常用于测量内科(n = 35)和外科(n = 21)治疗的结果。ehp还用于13项其他干预研究,29项非干预研究,32项心理测量/跨文化验证研究;6项诊断性研究,另外3项研究测量相关疾病的结果。它们主要用于在欧洲和北美进行的研究。总体而言,无论干预的性质如何,大多数妇女报告治疗后HRQoL有所改善。手术干预通常在最长的时间内产生显著的改善。也有证据表明,当参与者停止服药时,他们的EHP得分会恶化,这可能会强化药物治疗的暂时影响。年轻患者报告对其HRQoL的负面影响更大。进一步的证据使用经典测试理论来支持EHPs稳健的心理测量特性,包括可接受性、维度、信度、效度(包括跨文化)和反应性,特别是EHP-30。引人注目的是,使用基于锚定的方法,EHP-30反应性研究表明,干预后“控制和无力感”领域的平均变化最大,其次是“疼痛”。MMAT结果表明,除了五项研究外,论文的质量很好。由于纳入本综述的干预措施和论文的异质性,未进行meta分析。更广泛的意义:患有子宫内膜异位症的妇女面临一生的手术和/或药物干预,以保持病情得到控制。我们需要侵入性较小的治疗方法,以改善长期的生理和心理社会结果。EHP是可靠的、有效的、可接受的和反应灵敏的工具,但使用现代心理测量方法,在不同种族背景的妇女和常规临床护理的背景下,对EHP结果进行更多的评估将是有益的。考虑到EHP-5的简洁性,它可能是常规临床实践中最合适的版本,而更长的EHP-30提供了更多的粒度,更适合于研究。
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引用次数: 0
Genetic mechanisms of fertilization failure and early embryonic arrest: a comprehensive review. 受精失败和早期胚胎停滞的遗传机制:综述。
IF 14.8 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-01-03 DOI: 10.1093/humupd/dmad026
Yiqiu Wei, Jingxuan Wang, Rui Qu, Weiqian Zhang, Yiling Tan, Yanwei Sha, Lin Li, Tailang Yin
<p><strong>Background: </strong>Infertility and pregnancy loss are longstanding problems. Successful fertilization and high-quality embryos are prerequisites for an ongoing pregnancy. Studies have proven that every stage in the human reproductive process is regulated by multiple genes and any problem, at any step, may lead to fertilization failure (FF) or early embryonic arrest (EEA). Doctors can diagnose the pathogenic factors involved in FF and EEA by using genetic methods. With the progress in the development of new genetic technologies, such as single-cell RNA analysis and whole-exome sequencing, a new approach has opened up for us to directly study human germ cells and reproductive development. These findings will help us to identify the unique mechanism(s) that leads to FF and EEA in order to find potential treatments.</p><p><strong>Objective and rationale: </strong>The goal of this review is to compile current genetic knowledge related to FF and EEA, clarifying the mechanisms involved and providing clues for clinical diagnosis and treatment.</p><p><strong>Search methods: </strong>PubMed was used to search for relevant research articles and reviews, primarily focusing on English-language publications from January 1978 to June 2023. The search terms included fertilization failure, early embryonic arrest, genetic, epigenetic, whole-exome sequencing, DNA methylation, chromosome, non-coding RNA, and other related keywords. Additional studies were identified by searching reference lists. This review primarily focuses on research conducted in humans. However, it also incorporates relevant data from animal models when applicable. The results were presented descriptively, and individual study quality was not assessed.</p><p><strong>Outcomes: </strong>A total of 233 relevant articles were included in the final review, from 3925 records identified initially. The review provides an overview of genetic factors and mechanisms involved in the human reproductive process. The genetic mutations and other genetic mechanisms of FF and EEA were systematically reviewed, for example, globozoospermia, oocyte activation failure, maternal effect gene mutations, zygotic genome activation abnormalities, chromosome abnormalities, and epigenetic abnormalities. Additionally, the review summarizes progress in treatments for different gene defects, offering new insights for clinical diagnosis and treatment.</p><p><strong>Wider implications: </strong>The information provided in this review will facilitate the development of more accurate molecular screening tools for diagnosing infertility using genetic markers and networks in human reproductive development. The findings will also help guide clinical practice by identifying appropriate interventions based on specific gene mutations. For example, when an individual has obvious gene mutations related to FF, ICSI is recommended instead of IVF. However, in the case of genetic defects such as phospholipase C zeta1 (PLCZ1), acti
背景:不孕不育和流产是长期存在的问题。成功的受精和高质量的胚胎是持续妊娠的先决条件。研究证明,人类生殖过程的每个阶段都受到多个基因的调控,任何一个问题,在任何一步,都可能导致受精失败(FF)或早期胚胎停滞(EEA)。医生可以通过基因方法诊断FF和EEA的致病因素。随着单细胞RNA分析和全外显子组测序等新遗传技术的发展,为我们直接研究人类生殖细胞和生殖发育开辟了一条新途径。这些发现将有助于我们确定导致FF和EEA的独特机制,以便找到潜在的治疗方法。目的和基本原理:本综述的目的是汇编目前与FF和EEA相关的遗传知识,阐明相关机制,并为临床诊断和治疗提供线索。检索方法:PubMed用于检索1978年1月至2023年6月的相关研究文章和综述,主要集中在英文出版物上。搜索词包括受精失败、早期胚胎停滞、遗传、表观遗传学、全外显子组测序、DNA甲基化、染色体、非编码RNA和其他相关关键词。通过搜索参考文献列表确定了其他研究。这篇综述主要关注在人类身上进行的研究。然而,在适用的情况下,它也包含了动物模型的相关数据。结果是描述性的,没有评估个人研究质量。结果:在最初确定的3925份记录中,共有233篇相关文章被纳入最终审查。该综述概述了人类生殖过程中涉及的遗传因素和机制。系统综述了FF和EEA的遗传突变和其他遗传机制,如球精子症、卵母细胞活化失败、母体效应基因突变、合子基因组活化异常、染色体异常和表观遗传学异常。此外,该综述总结了不同基因缺陷治疗的进展,为临床诊断和治疗提供了新的见解。更广泛的意义:本综述中提供的信息将有助于开发更准确的分子筛查工具,利用人类生殖发育中的遗传标记和网络诊断不孕不育。研究结果还将有助于指导临床实践,根据特定基因突变确定适当的干预措施。例如,当一个个体有明显的与FF相关的基因突变时,建议使用ICSI而不是IVF。然而,在遗传缺陷如磷脂酶Czeta1(PLCZ1)、肌动蛋白样7A(ACTL7A)、肌动蛋白类9(ACTL9)和含有IQ基序的N(IQCN)的情况下,ICSI也可能无法受精。我们可以考虑将人工卵母细胞激活技术与ICSI结合起来,以提高受精率,降低金钱和时间成本。未来,通过干扰或补充相关基因,有望提高或恢复生育能力。
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Human Reproduction Update
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