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A blended preconception lifestyle programme for couples undergoing IVF: lessons learned from a multicentre randomised controlled trial 接受体外受精夫妇的混合孕前生活方式计划:来自多中心随机对照试验的经验教训
Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2023-01-01 DOI: 10.1093/hropen/hoad036
Tessy Boedt, Eline Dancet, Diane De Neubourg, Sofie Vereeck, Jan Seghers, Katleen Van der Gucht, Ben Van Calster, Carl Spiessens, Sharon Lie Fong, Christophe Matthys
Abstract STUDY QUESTION What is the effect of a blended preconception lifestyle programme on reproductive and lifestyle outcomes of couples going through their first 12 months of IVF as compared to an attention control condition? SUMMARY ANSWER This randomized controlled trial (RCT) was stopped prematurely because of the coronavirus disease 2019 (Covid-19) pandemic but the available data did not suggest that a blended preconception lifestyle programme could meaningfully affect time to ongoing pregnancy or other reproductive and lifestyle outcomes. WHAT IS KNOWN ALREADY Increasing evidence shows associations between a healthy lifestyle and IVF success rates. Lifestyle programmes provided through a mobile phone application have yet to be evaluated by RCTs in couples undergoing IVF. STUDY DESIGN, SIZE, DURATION A multicentre RCT (1:1) was carried out. The RCT started in January 2019 and was prematurely stopped because of the Covid-19 pandemic, leading to a reduced sample size (211 couples initiating IVF) and change in primary outcome (cumulative ongoing pregnancy to time to ongoing pregnancy). PARTICIPANTS/MATERIALS, SETTING, METHODS Heterosexual couples initiating IVF in five fertility clinics were randomized between an attention control arm and an intervention arm for 12 months. The attention control arm received treatment information by mobile phone in addition to standard care. The intervention arm received the blended preconception lifestyle (PreLiFe)-programme in addition to standard care. The PreLiFe-programme included a mobile application, offering tailored advice and skills training on diet, physical activity and mindfulness, in combination with motivational interviewing over the telephone. The primary outcome was ‘time to ongoing pregnancy’. Secondary reproductive outcomes included the Core Outcome Measures for Infertility Trials and IVF discontinuation. Changes in the following secondary lifestyle outcomes over 3 and 6 months were studied in both partners: diet quality, fruit intake, vegetable intake, total moderate to vigorous physical activity, sedentary behaviour, emotional distress, quality of life, BMI, and waist circumference. Finally, in the intervention arm, acceptability of the programme was evaluated and actual use of the mobile application part of the programme was tracked. Analysis was according to intention to treat. MAIN RESULTS AND THE ROLE OF CHANCE A total of 211 couples were randomized (105 control arm, 106 intervention arm). The hazard ratio of the intervention for time to ongoing pregnancy was 0.94 (95% CI 0.63 to 1.4). Little to no effect on other reproductive or lifestyle outcomes was identified. Although acceptability of the programme was good (6/10), considerable proportions of men (38%) and 9% of women did not actively use all the modules of the mobile application (diet, physical activity, or mindfulness). LIMITATIONS, REASONS FOR CAUTION The findings of this RCT should be considered exploratory, as the Covid-19 p
摘要研究问题:与注意控制条件相比,混合孕前生活方式计划对试管婴儿前12个月夫妇的生殖和生活方式结果有什么影响?由于2019冠状病毒病(Covid-19)大流行,该随机对照试验(RCT)提前停止,但现有数据并未表明混合孕前生活方式计划会对持续怀孕的时间或其他生殖和生活方式结果产生有意义的影响。越来越多的证据表明,健康的生活方式与试管婴儿成功率之间存在关联。通过手机应用程序提供的生活方式项目尚未通过随机对照试验对接受体外受精的夫妇进行评估。研究设计、规模、持续时间采用多中心随机对照试验(1:1)。该随机对照试验于2019年1月开始,由于Covid-19大流行而过早停止,导致样本量减少(211对夫妇开始试管婴儿),主要结果发生变化(累积持续妊娠到持续妊娠的时间)。参与者/材料、环境、方法在5家生育诊所开始试管婴儿的异性夫妇被随机分为注意控制组和干预组,为期12个月。注意控制组除了接受标准治疗外,还通过手机接收治疗信息。干预组除标准治疗外,还接受了混合孕前生活方式(PreLiFe)方案。“pre - life”项目包括一个移动应用程序,提供量身定制的饮食、体育活动和正念方面的建议和技能培训,并结合电话上的动机访谈。主要结果是“持续怀孕时间”。次要生殖结局包括不孕不育试验和试管婴儿中止的核心结局指标。在3个月和6个月的时间里,研究了夫妻双方在以下次要生活方式方面的变化:饮食质量、水果摄入量、蔬菜摄入量、总的中度到剧烈的体育活动、久坐行为、情绪困扰、生活质量、BMI和腰围。最后,在干预部分,评估了程序的可接受性,并跟踪了程序的移动应用部分的实际使用情况。按意向治疗进行分析。随机选取211对夫妇(对照组105对,干预组106对)。干预时间与持续妊娠的风险比为0.94 (95% CI 0.63 ~ 1.4)。对其他生殖或生活方式的影响微乎其微。尽管该程序的可接受性很好(6/10),但相当比例的男性(38%)和9%的女性并没有积极使用移动应用程序的所有模块(饮食、体育活动或正念)。该随机对照试验的结果应被视为探索性的,因为Covid-19大流行限制了它的能力,而且移动应用程序的实际使用率很低。研究结果的更广泛意义这是第一项多中心随机对照试验,评估接受体外受精的妇女及其伴侣的混合孕前生活方式方案对生殖和生活方式结果的影响。这项探索性随机对照试验强调了进一步研究孕前生活方式方案的最佳干预特征和实际使用,以及评估有效性的随机对照试验的必要性。研究经费/竞争利益(S)由比利时弗兰德斯研究基金会(two - tbm;参考:T005417N)。没有竞争利益需要申报。试验注册号ClinicalTrials.gov标识符:NCT03790449试验注册日期2018年12月31日第一位患者入组日期2019年1月2日
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引用次数: 0
The role of iron in the pathogenesis of endometriosis: a systematic review. 铁在子宫内膜异位症发病机制中的作用:系统综述。
Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2023-01-01 DOI: 10.1093/hropen/hoad033
James Wyatt, Sean M Fernando, Simon George Powell, Christopher J Hill, Ilyas Arshad, Chris Probert, Shakil Ahmed, Dharani K Hapangama
<p><strong>Study question: </strong>What is the role of iron in the pathophysiology of endometriosis?</p><p><strong>Summary answer: </strong>Iron excess is demonstrated wherever endometriotic tissues are found and is associated with oxidative stress, an inflammatory micro-environment, and cell damage; the iron-mediated oxidative stress is independently linked to subfertility, symptom severity, and malignant transformation.</p><p><strong>What is known already: </strong>Iron is found in excess in endometriotic tissues, and multiple mechanisms have been studied and posited to explain this. It is clear that iron excess plays a vital role in promoting oxidative stress and cell damage. The evidence base is large, but no comprehensive reviews exist to summarize our understanding and highlight the overarching themes to further our understanding and suggest future directions of study for the field.</p><p><strong>Study design size duration: </strong>This systematic review with a thematic analysis retrieved studies from the PubMed, Embase, Web of Science, and Cochrane Library databases and searches were conducted from inception through to August 2022. Human and animal studies published in the English language were included and identified using a combination of exploded MeSH terms ('Iron' and 'Endometriosis') and free-text search terms ('Iron', 'Ferric', 'Ferrous', 'Endometriosis', 'Endometrioma').</p><p><strong>Participants/materials setting methods: </strong>This review was reported in accordance with the PRISMA guidelines. All studies reporting original data concerning the role of iron or iron complexes in the pathophysiology of endometriosis were included. Studies that did not report original data or provided a review of the field were excluded. Bias analysis was completed for each included study by using the Newcastle-Ottawa scoring system.</p><p><strong>Main results and the role of chance: </strong>There were 776 records identified and these were screened down to 53 studies which met the eligibility criteria, including 6 animal and 47 human studies, with 3556 individual participants. Iron excess is demonstrated in various tissues and fluids, including ovarian endometriomas, ovarian follicles, ectopic endometriotic lesions, and peritoneal fluid. Markers of oxidative stress are strongly associated with high iron levels, and aberrant expression of iron-transport proteins has been demonstrated. Abnormal resistance to ferroptosis is likely. Iron-mediated oxidative stress is responsible for a pro-inflammatory micro-environment and is linked to subfertility, symptom severity, and, possibly, malignant transformation.</p><p><strong>Limitations reasons for caution: </strong>A minority of the included studies were of objectively low quality with a high risk of bias and may lead to misleading conclusions. Additionally, multiple studies failed to appropriately characterize the included patients by known confounding variables, such as menstrual cycle phase, which ma
研究问题:铁在子宫内膜异位症病理生理中的作用是什么?总结回答:无论子宫内膜异位症组织在哪里,铁含量都会过量,并与氧化应激、炎症微环境和细胞损伤有关;铁介导的氧化应激与低生育能力、症状严重程度和恶性转化独立相关。已知情况:在子宫内膜异位症组织中发现了过量的铁,已经研究并提出了多种机制来解释这一点。很明显,铁过量在促进氧化应激和细胞损伤中起着至关重要的作用。证据基础很大,但没有全面的综述来总结我们的理解,并强调总体主题,以进一步我们的理解,并为该领域的未来研究方向提出建议。研究设计规模持续时间:本系统综述采用专题分析,检索了PubMed、Embase、Web of Science和Cochrane图书馆数据库的研究,检索时间从开始到2022年8月。用英语发表的人类和动物研究被包括在内,并使用爆炸MeSH术语(“铁”和“子宫内膜异位症”)和自由文本搜索术语(“铁”、“铁”、“铁”、“子宫内膜异位症”、“子宫内膜异位症”)的组合进行识别。受试者/材料设置方法:本综述按照PRISMA指南报道。所有报道铁或铁复合物在子宫内膜异位症病理生理作用的原始数据的研究都被纳入。未报告原始数据或未提供该领域综述的研究被排除在外。采用纽卡斯尔-渥太华评分系统对每个纳入的研究进行偏倚分析。主要结果和偶然性的作用:共有776条记录被确定,这些记录被筛选到53项符合资格标准的研究,包括6项动物研究和47项人类研究,共有3556名个体参与者。铁过量存在于多种组织和液体中,包括卵巢子宫内膜异位症、卵巢卵泡、异位子宫内膜病变和腹膜液。氧化应激标志物与高铁水平密切相关,铁转运蛋白的异常表达已被证实。对铁下垂的异常抵抗是可能的。铁介导的氧化应激负责促炎微环境,与生育能力低下、症状严重以及可能的恶性转化有关。局限性:少数纳入的研究客观上质量较低,存在高偏倚风险,可能导致误导性结论。此外,多项研究未能通过已知的混杂变量(如月经周期)适当地描述纳入的患者,这可能会对研究结果产生偏倚。研究结果的更广泛意义:目前的文献描述了异常铁力学和随后的氧化应激在子宫内膜异位症中的核心作用。这可能是铁过量至少部分负责的持续和增殖异位子宫内膜病变。因此,铁力学代表了一个有吸引力的新治疗靶点,包括铁螯合剂或铁氧化应激途径的效应器。在我们目前的理解中存在显著的差距,这篇综述强调并推荐了几个进一步研究的主题。这些包括铁螯合的作用,对铁下沉的抵抗,铁过量与局部缺氧的关系,子宫内膜异位症的全身铁病理生理,以及氧化应激在恶性转化中的作用。研究资金/竞争利益:J.W.和S.G.P.由利物浦大学医院NHS基金会信托的临床奖学金支持。没有为完成这项工作要求或需要额外的经费。C.J.H.得到了妇女福利项目补助金(RG2137)的支持。D.K.H.由妇女福利项目资助(RG2137)和MRC临床研究培训奖学金(MR/V007238/1)支持。作者无利益冲突需要申报。注册编号:该协议已于2021年8月在PROSPERO数据库中前瞻性注册(CRD42021272818)。
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引用次数: 2
Reply to: Anti-anonymity should not be taken more seriously than other positions on gamete donation. 回复:在配子捐赠问题上,反匿名不应该比其他立场更严肃。
Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2023-01-01 DOI: 10.1093/hropen/hoac060
Daniel Groll
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引用次数: 0
Caution is needed when communicating analyses based on an apple to orange comparison. 在交流基于苹果与橘子比较的分析时,需要谨慎。
Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2023-01-01 DOI: 10.1093/hropen/hoad016
Birgit Alsbjerg, Peter Humaidan
It was with great interest that we read ‘The effect of frozen embryo transfer regimen on the association between serum progesterone and live birth: a multi-centre prospective cohort study (ProFET)’ by Melo et al. (2022). From their data, the authors concluded that overall serum progesterone levels (P4) <7.8 ng/ml are associated with reduced odds of live birth in frozen embryo transfer (FET). Interestingly, the authors previously published a meta-analysis (Melo et al., 2021) based on several cohort studies of HRT-FET cycles using vaginal progesterone for luteal phase support and reporting a higher P4 cut-off <10 ng/ml for the reproductive outcome. Thus, in that analysis, higher serum P4 levels were associated with increased ongoing pregnancy or live birth rates (LBRs). An important question to ask in relation to the newest publication by Melo et al. (2022) would be: is this suggested new cut-off of serum P4 of 7.8 ng/ml more accurate than 10 ng/ml, and is this cut-off applicable to all FET protocols? Reading the publication carefully reveals that the present study was powered to 900 FET cycles; however, only a total of 398 cycles were included in the final analysis. Furthermore, the cohort of FET protocols was very heterogeneous, including HRT-FET, true natural cycle (t-NC), and modified natural cycle (m-NC), in which ovulation is induced with a trigger bolus of hCG. In this context, we have to bear in mind that the FET protocols mentioned are very different in terms of basic endocrinology, first and foremost when considering serum P4. Thus, the natural cycle has a circadian luteal phase progesterone pattern due to the endogenous production of progesterone from the corpus luteum and importantly, in the new Melo et al. (2022) study, a huge variation in the type of ‘NC FET’ protocols was allowed. Thus, different hCG-trigger doses (5000 vs 6500 IE) were used which will definitely have an impact on circulating luteal P4; moreover, in some cycles, no hCG trigger (t-NC) was used and some cycles had vaginal progesterone support whereas others did not. Finally, different dosing and types of vaginal micronized progesterone were used (CyclogestR , UtrogestanR ). Altogether, within a cohort of 45 ‘NC FET’, there might have been as many as nine different combinations; importantly, these differences will invariably result in significant differences in luteal P4 profiles. Furthermore, in the cohort of HRT-FET cycles, we also learn that important differences were allowed in terms of different vaginal micronized progesterone products, differences in dosing regimen and differences in no use or use of a combination of subcutaneous (s.c.) progesterone (LubionR ), 25 mg once daily or twice daily. For monitoring, the authors state that blood sampling was performed 4–6 h after the last administration of exogenous progesterone. Again, the reader might ask, what does ‘approximately’ mean? One hour, two hours—or more? Timing of luteal phase blood sampling is crucial, espe
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引用次数: 1
ESGO/ESHRE/ESGE Guidelines for the fertility-sparing treatment of patients with endometrial carcinoma. 子宫内膜癌患者保留生育能力治疗的ESGO/ESHRE/ESGE指南
Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2023-01-01 DOI: 10.1093/hropen/hoac057
Alexandros Rodolakis, Giovanni Scambia, François Planchamp, Maribel Acien, Attilio Di Spiezio Sardo, Martin Farrugia, Michael Grynberg, Maja Pakiz, Kitty Pavlakis, Nathalie Vermeulen, Gianfranco Zannoni, Ignacio Zapardiel, Kirsten Louise Tryde Macklon
<p><strong>Study question: </strong>How should fertility-sparing treatment of patients with endometrial carcinoma be performed?</p><p><strong>Summary answer: </strong>Forty-eight recommendations were formulated on fertility-sparing treatment of patients with endometrial carcinoma.</p><p><strong>What is known already: </strong>The standard surgical treatment of endometrial carcinoma consisting of total hysterectomy with bilateral salpingo-oophorectomy drastically affects the quality of life of patients and creates a challenge for clinicians. Recent evidence-based guidelines of the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy & Oncology (ESTRO) and the European Society of Pathology (ESP) provide comprehensive guidelines on all relevant issues of diagnosis and treatment in endometrial carcinoma in a multidisciplinary setting. While addressing also work-up for fertility preservation treatments and the management and follow-up for fertility preservation, it was considered relevant to further extend the guidance on fertility-sparing treatment.</p><p><strong>Study design size duration: </strong>A collaboration was set up between the ESGO, the European Society of Human Reproduction and Embryology (ESHRE) and the European Society for Gynaecological Endoscopy (ESGE), aiming to develop clinically relevant and evidence-based guidelines focusing on key aspects of fertility-sparing treatment in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide.</p><p><strong>Participants/materials setting methods: </strong>ESGO/ESHRE/ESGE nominated an international multidisciplinary development group consisting of practising clinicians and researchers who have demonstrated leadership and expertise in the care and research of endometrial carcinoma (11 experts across Europe). To ensure that the guidelines are evidence-based, the literature published since 2016, identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgement was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 95 independent international practitioners in cancer care delivery and patient representatives.</p><p><strong>Main results and the role of chance: </strong>The multidisciplinary development group formulated 48 recommendations in four sections; patient selection, tumour clinicopathological characteristics, treatment and special issues.</p><p><strong>Limitations reasons for caution: </strong>Of the 48 recommendations, none could be based on level I evidence and only 16 could be based on level II evidence, implicating that 66% of the recommendations are supported only by observational data, professional experience and consensus of the development group.</p><p><strong>Wider implication
研究问题:子宫内膜癌患者应如何进行保留生育能力的治疗?总结回答:对子宫内膜癌患者保留生育能力的治疗提出了48条建议。已知情况:子宫内膜癌的标准手术治疗包括全子宫切除术和双侧输卵管-卵巢切除术,这极大地影响了患者的生活质量,给临床医生带来了挑战。最近,欧洲妇科肿瘤学会(ESGO)、欧洲放射与肿瘤学会(ESTRO)和欧洲病理学会(ESP)的循证指南为多学科背景下子宫内膜癌诊断和治疗的所有相关问题提供了全面的指南。在处理保留生育能力治疗的后继工作和保留生育能力的管理和后续工作的同时,认为有必要进一步扩大保留生育能力治疗的指导。研究设计规模持续时间:ESGO、欧洲人类生殖与胚胎学会(ESHRE)和欧洲妇科内窥镜学会(ESGE)之间建立了一项合作,旨在制定临床相关的循证指南,重点关注生育保留治疗的关键方面,以提高欧洲和全球子宫内膜癌女性的护理质量。参与者/材料设置方法:ESGO/ESHRE/ESGE提名了一个国际多学科发展小组,由在子宫内膜癌的护理和研究方面表现出领导力和专业知识的执业临床医生和研究人员组成(来自欧洲的11名专家)。为了确保指南以证据为基础,对2016年以来发表的文献进行了审查和批判性评估,这些文献是通过系统检索确定的。在没有任何明确的科学证据的情况下,判断是基于专业经验和发展小组的共识。因此,该指南是基于现有的最佳证据和专家协议。在发表之前,该指南由95名独立的国际癌症护理从业人员和患者代表进行了审查。主要结果和机遇的作用:多学科发展小组在四个部分提出了48条建议;患者选择,肿瘤临床病理特征,治疗和特殊问题。谨慎的局限性:在48条建议中,没有一条可基于一级证据,只有16条可基于二级证据,这意味着66%的建议仅由观察数据、专业经验和发展小组的共识支持。研究结果的更广泛意义:这些建议为照顾子宫内膜癌妇女的专业人员提供指导,包括但不限于妇科肿瘤学、肿瘤生育、生殖外科、内窥镜检查、保守手术和组织病理学领域的专业人员,并将有助于为这一具有挑战性的临床情况提供全面和多学科的方法。研究经费/竞争利益:与开发过程有关的所有费用均由ESGO、ESHRE和ESGE基金支付。没有外部资金支持开发过程或手稿制作。G.S.获得了MSD Italia S.r.l、Storz、Bayer、Astrazeneca、Metronic、TESARO Bio Italy S.r.l和Johnson & Johnson顾问委员会的资助,并获得了Clovis Oncology Italy S.r.l的讲座荣誉。M.G.还获得了Gedeon Richter和Merck顾问委员会的报告。其他作者没有报告任何利益冲突。免责声明:本文件代表ESHRE、ESGO和ESGE的观点,是相关利益相关者之间达成共识的结果,并在相关情况下基于准备时可用的科学证据。这些建议应用于宣传和教育目的。它们不应被解释为制定护理标准,也不应被视为包括所有适当的护理方法,也不应排除其他合理指导以获得相同结果的护理方法。它们不能取代对每个个体表现的临床判断,也不能取代基于地点和设施类型的变化。
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引用次数: 4
Spermatogenesis after gonadotoxic childhood treatment: follow-up of 12 patients. 儿童期促性腺毒素治疗后精子发生:12例患者的随访。
Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2023-01-01 DOI: 10.1093/hropen/hoad029
E Delgouffe, A Braye, V Vloeberghs, I Mateizel, C Ernst, A Ferster, C Devalck, H Tournaye, I Gies, E Goossens

Study question: What is the long-term impact of presumed gonadotoxic treatment during childhood on the patient's testicular function at adulthood?

Summary answer: Although most patients showed low testicular volumes and some degree of reproductive hormone disruption 12.3 (2.3-21.0) years after gonadotoxic childhood therapy, active spermatogenesis was demonstrated in the semen sample of 8 out of the 12 patients.

What is known already: In recent decades, experimental testicular tissue banking programmes have been set up to safeguard the future fertility of young boys requiring chemo- and/or radiotherapy with significant gonadotoxicity. Although the risk of azoospermia following such therapies is estimated to be high, only limited long-term data are available on the reproductive potential at adulthood.

Study design size duration: This single-centre prospective cohort study was conducted between September 2020 and February 2023 and involved 12 adult patients.

Participants/materials setting methods: This study was carried out in a tertiary care centre and included 12 young adults (18.1-28.3 years old) who had been offered testicular tissue banking prior to gonadotoxic treatment during childhood. All patients had a consultation and physical examination with a fertility specialist, a scrotal ultrasound to measure the testicular volumes and evaluate the testicular parenchyma, a blood test for assessment of reproductive hormones, and a semen analysis.

Main results and the role of chance: Testicular tissue was banked prior to the gonadotoxic treatment for 10 out of the 12 included patients. Testicular volumes were low for 9 patients, and 10 patients showed some degree of reproductive hormone disruption. Remarkably, ongoing spermatogenesis was demonstrated in 8 patients at a median 12.3 (range 2.3-21.0) years post-treatment.

Limitations reasons for caution: This study had a limited sample size, making additional research with a larger study population necessary to verify these preliminary findings.

Wider implications of the findings: These findings highlight the need for multicentric research with a larger study population to establish universal inclusion criteria for immature testicular tissue banking.

Study funding/competing interests: This study was conducted with financial support from the Research Programme of the Research Foundation-Flanders (G010918N), Kom Op Tegen Kanker, and Scientific Fund Willy Gepts (WFWG19-03). The authors declare no competing interests.

Trial registration number: NCT04202094; https://clinicaltrials.gov/ct2/show/NCT04202094?id=NCT04202094&draw=2&rank=1 This study was registered on 6 December 2019, and the first patient was enrolled on 8 September 2020.

研究问题:儿童期假定的促性腺毒素治疗对患者成年后睾丸功能的长期影响是什么?虽然大多数患者在儿童期促性腺毒素治疗后12.3(2.3-21.0)年表现出睾丸体积低和一定程度的生殖激素紊乱,但12例患者中有8例的精液样本显示出活跃的精子发生。已知情况:近几十年来,已经建立了实验性睾丸组织库计划,以保障需要化疗和/或放射治疗的年轻男孩未来的生育能力,这些男孩具有明显的促性腺毒性。虽然这些治疗后无精子症的风险估计很高,但只有有限的关于成年期生殖潜力的长期数据。研究设计规模持续时间:该单中心前瞻性队列研究于2020年9月至2023年2月进行,涉及12名成年患者。参与者/材料设置方法:本研究在三级保健中心进行,包括12名年轻成年人(18.1-28.3岁),他们在儿童时期接受促性腺毒素治疗之前接受了睾丸组织库。所有患者都接受了生育专家的咨询和体格检查,进行了阴囊超声检查以测量睾丸体积和评估睾丸实质,进行了血液检查以评估生殖激素,并进行了精液分析。主要结果和偶然性的作用:12例患者中有10例在使用促性腺激素治疗前已将睾丸组织储存起来。9例患者睾丸体积低,10例患者出现不同程度的生殖激素紊乱。值得注意的是,在治疗后中位12.3年(范围2.3-21.0年),8名患者显示出持续的精子发生。注意事项:本研究样本量有限,需要对更大的研究人群进行额外的研究来验证这些初步发现。研究结果的更广泛意义:这些发现强调需要多中心研究和更大的研究人群来建立未成熟睾丸组织库的普遍纳入标准。研究经费/竞争利益:本研究由弗兰德斯研究基金会(G010918N)、Kom Op Tegen Kanker和科学基金Willy Gepts (WFWG19-03)的研究计划资助。作者声明没有利益冲突。试验注册号:NCT04202094;https://clinicaltrials.gov/ct2/show/NCT04202094?id=NCT04202094&draw=2&rank=1本研究于2019年12月6日注册,第一位患者于2020年9月8日入组。
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引用次数: 1
The impact of small and asymptomatic intramural and subserosal fibroids on female fertility: a case-control study. 无症状的小肌瘤对女性生育能力的影响:一项病例对照研究。
Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2023-01-01 DOI: 10.1093/hropen/hoac056
Valentina Bonanni, Marco Reschini, Irene La Vecchia, Marta Castiglioni, Ludovico Muzii, Paolo Vercellini, Edgardo Somigliana
<p><strong>Study question: </strong>Do small and asymptomatic intramural and subserosal uterine fibroids affect female fertility?</p><p><strong>Summary answer: </strong>Small and asymptomatic fibroids that do not encroach the endometrial cavity appear to not markedly affect female fertility.</p><p><strong>What is known already: </strong>The available evidence on uterine fibroids and fertility is limited. Most information has been obtained in IVF settings by comparing the success in women affected and not affected by fibroids. These studies have shown a detrimental effect of submucosal and possibly intramural fibroids. However, this study design provides information only on embryo implantation, not on female fertility in general.</p><p><strong>Study design size duration: </strong>A retrospective observational case-control study on 200 women whose partner was diagnosed with severe male infertility and 200 women with unexplained infertility was conducted. If the null hypothesis (that fibroids do not affect fertility) is valid, one would expect a similar prevalence of fibroids in the two study groups. Conversely, if fibroids do impact fertility, one would expect a higher prevalence among women with unexplained infertility. The study was carried out at the Infertility Unit of the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico covering a 5-year period between January 2014 and June 2020.</p><p><strong>Participants/materials setting methods: </strong>We retrospectively recruited women seeking pregnancy whose partner was repeatedly documented to have a sperm concentration below 1 million/ml and matched them by age and study period to a group of women with unexplained infertility. The latter group of women was considered as a case group (infertile subjects), while the former group of women was considered as a control group (reflecting the general female population). Women with fibroids could be included in both study groups; only those with submucosal lesions were excluded.</p><p><strong>Main results and the role of chance: </strong>Fibroids were diagnosed in 31 women (16%) with unexplained infertility and in 32 women (16%) with severe male factor infertility. The adjusted odds ratio of carrying fibroids in women with unexplained infertility was 0.91 (95% CI: 0.52-1.58). Subgroup analyses according to number, dimension and location of fibroids failed to highlight an increased risk of infertility in any group.</p><p><strong>Limitations reasons for caution: </strong>This is a retrospective study and some inaccuracies in fibroids detection cannot be ruled out. Moreover, the relatively small sample size hampers robust subgroup analyses. Even though we excluded women with patent causes of infertility, some women with specific causes of infertility could have been included among controls (yet are expected to account for <10% of the group).</p><p><strong>Wider implications of the findings: </strong>This study suggests that small fibroids that do not en
研究问题:小而无症状的子宫壁内和浆膜下肌瘤会影响女性生育能力吗?概要回答:小而无症状的肌瘤不侵犯子宫内膜腔,似乎不明显影响女性生育能力。已知情况:关于子宫肌瘤和生育能力的现有证据有限。大多数信息是通过比较受子宫肌瘤影响的妇女和未受子宫肌瘤影响的妇女的成功而获得的。这些研究显示了粘膜下和可能的壁内肌瘤的有害影响。然而,这项研究设计只提供了胚胎植入的信息,而不是一般的女性生育能力。研究设计规模持续时间:回顾性观察性病例对照研究,对200名配偶诊断为严重男性不育症的女性和200名不明原因不育症的女性进行研究。如果原假设(肌瘤不影响生育)是有效的,人们会期望在两个研究组中有相似的肌瘤患病率。相反,如果子宫肌瘤确实影响生育能力,那么在不明原因不孕的女性中发病率会更高。该研究是在IRCCS Ca' Granda Ospedale Maggiore Policlinico基金会的不孕症部门进行的,为期5年,从2014年1月到2020年6月。参与者/材料设置方法:我们回顾性地招募了寻求怀孕的女性,其伴侣的精子浓度多次低于100万/ml,并根据年龄和研究期间将她们与一组原因不明的不孕症女性进行匹配。后一组妇女被视为病例组(不育受试者),而前一组妇女被视为对照组(反映一般女性人口)。患有肌瘤的女性可以被纳入两个研究组;仅排除粘膜下病变的患者。主要结果和偶然性的作用:31例(16%)不明原因不孕症患者诊断为肌瘤,32例(16%)严重男性因素不孕症患者诊断为肌瘤。不明原因不孕妇女携带肌瘤的校正优势比为0.91 (95% CI: 0.52-1.58)。根据子宫肌瘤的数量、大小和位置进行亚组分析,没有发现任何一组的不孕风险增加。局限性:这是一项回顾性研究,不能排除子宫肌瘤检测中的一些不准确性。此外,相对较小的样本量妨碍了稳健的亚组分析。尽管我们排除了有明显不孕原因的女性,但一些有特殊不孕原因的女性可能被包括在对照组中(但预计会解释研究结果的更广泛含义:这项研究表明,不侵犯子宫内膜腔的小肌瘤不会显著影响女性的生育能力。)这一信息在咨询患有小肌瘤的不孕妇女和其他不显著的诊断检查时具有临床相关性。手术仍可考虑,但仅限于选定的病例。研究经费/竞争利益:本研究部分由意大利卫生部资助:当前研究IRCCS。E.S.报告Ferring的资助,默克的资助和个人费用,以及Theramex在提交工作之外的资助和个人费用。所有其他作者没有任何竞争利益要申报。试验注册号:无。
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引用次数: 1
Stimulating fertility awareness: the importance of getting the language right. 激发生育意识:正确使用语言的重要性。
Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2023-01-01 DOI: 10.1093/hropen/hoad009
H Mertes, J Harper, J Boivin, M Ekstrand Ragnar, B Grace, M Moura-Ramos, S Rautakallio-Hokkanen, M Simopoulou, K Hammarberg, On Behalf Of The International Reproductive Health Education Collaboration Irhec

While education about fertility is not intrinsically controversial, finding the right language to communicate the topic can be challenging, as there are several risks of unintended negative effects such as dissonance, anxiety, culpability, and stigma due to social norming. In this article, we share some of our learnings from promoting fertility awareness in the hope that they will inspire further debate and research on this topic. Starting from the ethical principles of respect for reproductive autonomy, avoiding harm (in terms of stigma or anxiety) and inclusivity, we have formulated five recommendations: (i) frame fertility awareness messages with (reproductive) autonomy in mind and aim to be inclusive of those who do not represent the traditional nuclear family; (ii) be empathetic and steer clear of blame; (iii) avoid scaremongering and offer a positive angle; (iv) give due consideration to both women and men in fertility health messaging; and (v) tailor the messages to particular contexts and audiences and develop resources in close collaboration with the target groups.

虽然关于生育的教育本身并没有争议,但找到合适的语言来传达这个话题可能是一项挑战,因为有一些意想不到的负面影响的风险,比如社会规范带来的不和谐、焦虑、罪责和耻辱。在这篇文章中,我们分享了我们在提高生育意识方面的一些经验,希望它们能激发对这一主题的进一步讨论和研究。从尊重生殖自主、避免伤害(在耻辱或焦虑方面)和包容性的伦理原则出发,我们制定了五项建议:(i)将(生殖)自主作为生育意识信息的框架,旨在包容那些不代表传统核心家庭的人;(ii)要有同理心,避免责备;(iii)避免危言耸听,并提供积极的角度;㈣在生育保健信息方面适当考虑到妇女和男子;㈤根据具体情况和受众定制信息,并与目标群体密切合作开发资源。
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引用次数: 2
Anti-anonymity should not be taken more seriously than other positions on gamete donation. 反匿名不应该比其他配子捐赠的立场更严肃。
Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2023-01-01 DOI: 10.1093/hropen/hoac059
Guido Pennings
Sir, In a recent response to my debate article (Pennings, 2022) on the forgotten group of donor-conceived persons (DCPs), Daniel Groll intended to show that my claim that ‘people who accept the antianonymity position should also accept the anti-donation position’ (the ‘equivalence argument’) is wrong (Groll, 2022). However, I did not make that claim (Pennings, 2022). Most of his argument is directed against a ‘straw man’ construction that makes a much stronger claim than the one I actually made. This ‘rephrasing’ of my main point makes it relatively easy to score. I (merely) argued that the anti-donation position should be recognized as equivalent to the anti-anonymity position as it is supported by the same type of arguments. This is a weaker claim that assumes no logical or dialectical pressure from one position to another. The reply offered by Dr Groll to that point is far from clear. He acknowledges, and I fully agree with him on that point, that the voices of DCPs have no epistemic authority. Lived experience cannot ground epistemic authority on many different aspects of gamete donation such as parental responsibility or the importance of genetic information. He concludes that we should not defer to the views of the DCPs but that we should take them very seriously. The problem is that he does not explain what ‘taking views very seriously’ means. But the problem goes deeper than that. When he recognizes that the views of DCPs have no special epistemic authority, he needs to explain why we should, nevertheless, take these views very seriously. He gives four reasons. One reason is that their voices have been comparatively absent. However, that cannot be a justification to why we should include these views, or any other view for that matter. Another reason is that we cannot get access to these views without asking the DCPs. That is correct, but the question was why (not how) we should take these views into account in the first place. A further reason is that the DCPs did not voluntarily participate in their conception. However, Dr Groll recognizes that this is the case for everyone, not just the DCPs. This lack of voluntariness creates an asymmetry between the procreators and the procreated. Again, although correct, no explanation is offered about what the implications of this asymmetry are, for DCPs and all other people. So that leaves us with the remaining reason: DCPs have a substantial interest. I accept this reason and I also believe that we need to talk to the DCPs in order to find out what these interests are. DCPs who believe that they are harmed because of a rule or measure that is part of the practice of gamete donation have a strong reason to try to change the rule or measure to avoid harm. However, not only are there several parties involved (DCPs, intended parents, donors), but within each party there are different opinions. All of these parties have a substantial but differing interest. As I have argued, the harm and interest are c
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引用次数: 0
Mind the mechanical strength: tailoring a 3D matrix to encapsulate isolated human preantral follicles. 注意机械强度:定制一个3D矩阵来封装孤立的人类腔前卵泡。
Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2023-01-01 DOI: 10.1093/hropen/hoad004
Arezoo Dadashzadeh, Saeid Moghassemi, Alexis Peaucelle, Carolina M Lucci, Christiani A Amorim
<p><strong>Study question: </strong>Would a hydrogel with similar mechanical properties to the human ovarian cortex support preantral follicle development?</p><p><strong>Summary answer: </strong>Yes, our tailored PEGylated fibrin hydrogel was shown to significantly improve follicle growth <i>in vitro.</i></p><p><strong>What is known already: </strong>One of the main challenges in developing an engineered ovary is to provide a 3D matrix that supports the follicle architecture and the interaction between granulosa cells and the oocyte as they are essential for folliculogenesis. Thanks to its biocompatibility and bioactivity, fibrin has been employed to fabricate a 3D matrix to encapsulate ovarian follicles. However, follicles lose their physical support within a few days owing to rapid fibrin degradation. Therefore, different strategies, including physical and chemical modifications, have been developed to enhance the stability of fibrin.</p><p><strong>Study design size duration: </strong>By developing a matrix made of a synthetic (polyethylene glycol: PEG) and natural polymer (fibrin), we aimed to overcome fibrin degradation by the chemical reaction of PEGylation and tailor a PEGylated fibrin hydrogel formulation with mechanical strength similar to the ovarian cortex in women of reproductive age. To this end, response surface methodology was employed to obtain a tailored formulation of PEGylated fibrin. This hydrogel was then tested to encapsulate and support isolated human preantral follicles <i>in vitro.</i></p><p><strong>Participants/materials setting methods: </strong>A PEGylated fibrin formulation was tailored using mathematical modeling software to mimic the mechanical properties of human ovarian tissue at reproductive age. Human preantral follicles were isolated from 11 patients of reproductive age and encapsulated in the tailored hydrogels, which were cultured <i>in vitro</i> for 4 or 7 days. Follicle survival and diameter were assessed on Days 1 and 7. Furthermore, the follicles were subjected to confocal microscopy to evaluate their growth (Ki67 staining) on Day 7 and analyze cell-cell communication (connexin 43 and transzonal projection staining) on Day 4.</p><p><strong>Main results and the role of chance: </strong>In this study, mathematical modeling was applied to achieve the biomechanically tailored PEGylated fibrin formulation by targeting the specific goal of 3178 ± 245 Pascal, Young's modulus of ovarian cortical tissue in reproductive-age women. Our results demonstrated that the PEGylated fibrin hydrogel consisting of 39.06 mg/ml of PEGylated fibrinogen and 50.36 IU/ml of thrombin was the optimum condition with the desirability of 97.5%. This tailored hydrogel yielded a high follicle survival rate (83%) after 7 days of <i>in vitro</i> culture and supported its development up to the secondary stage. Follicle growth was confirmed by the presence of Ki67-positive granulosa cells on Day 7. Additionally, connexin 43 and Phalloidin stai
研究问题:与人类卵巢皮质具有相似机械特性的水凝胶是否能支持腔前卵泡发育?概要回答:是的,我们量身定制的聚乙二醇化纤维蛋白水凝胶在体外被证明能显著改善卵泡生长。已知情况:开发工程化卵巢的主要挑战之一是提供3D基质来支持卵泡结构以及颗粒细胞和卵母细胞之间的相互作用,因为它们对卵泡形成至关重要。由于其生物相容性和生物活性,纤维蛋白已被用于制造3D基质来包裹卵巢卵泡。然而,由于纤维蛋白的快速降解,卵泡在几天内就失去了它们的物理支持。因此,不同的策略,包括物理和化学修饰,已经开发,以提高纤维蛋白的稳定性。研究设计规模持续时间:通过开发由合成(聚乙二醇:PEG)和天然聚合物(纤维蛋白)制成的基质,我们旨在通过聚乙二醇化的化学反应克服纤维蛋白降解,并定制聚乙二醇化纤维蛋白水凝胶配方,其机械强度与育龄妇女卵巢皮质相似。为此,采用响应面法获得了聚乙二醇化纤维蛋白的定制配方。然后测试该水凝胶在体外封装和支持分离的人腔前卵泡。参与者/材料设置方法:使用数学建模软件定制聚乙二醇化纤维蛋白配方,以模拟育龄人类卵巢组织的力学特性。从11例育龄患者中分离出人腔前卵泡,包封在定制的水凝胶中,体外培养4天或7天。在第1天和第7天评估卵泡存活率和直径。第7天用共聚焦显微镜观察毛囊的生长情况(Ki67染色),第4天用连接蛋白43和跨区投影染色分析细胞间通讯。主要结果和随机因素的作用:本研究采用数学模型,以育龄女性卵巢皮质组织的杨氏模量(3178±245)为目标,实现生物力学量身定制的聚乙二醇化纤维蛋白配方。结果表明,聚乙二醇化纤维蛋白原39.06 mg/ml和凝血酶50.36 IU/ml的聚乙二醇化纤维蛋白水凝胶为最佳制备条件,适宜率为97.5%。这种定制水凝胶在体外培养7天后获得了很高的卵泡存活率(83%),并支持其发展到二期。第7天出现ki67阳性颗粒细胞,证实卵泡生长。此外,连接蛋白43和Phalloidin染色显示颗粒细胞与卵母细胞之间的连接保留。大规模数据:无。局限性:在本研究中,我们定制的水凝胶仅在体外测试,与生理环境不一样。在定制的水凝胶中对卵泡进行包封和移植后进行研究是至关重要的,这将是我们研究的下一步。研究结果的更广泛意义:本研究的结果介绍了一种适合的生物材料,类似于育龄妇女卵巢皮质,在生物力学特性方面可以包裹人类腔前卵泡。这种生物材料允许卵泡径向生长并保持其活力。此外,聚乙二醇化改善了纤维蛋白的稳定性和卵泡的物理支持。研究经费/竞争利益:本研究由Louvain基金会资助(博士奖学金授予s.m.,作为Frans Heyes先生遗产的一部分,博士奖学金授予A.D.,作为Ilse Schirmer夫人遗产的一部分)。作者声明没有利益冲突。
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引用次数: 1
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Human reproduction open
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