Reproductive biomedicine online最新文献

英文中文

Comparative proteomic analysis of receptive and non-receptive endometria-derived uterine fluid suggests a panel for endometrial receptivity assessment 接受性和非接受性子宫内膜来源的子宫液的比较蛋白质组学分析建议一个评估子宫内膜容受性的小组。

IF 3.5 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Reproductive biomedicine online

Pub Date : 2025-12-01 DOI: 10.1016/j.rbmo.2025.105083

Farnoosh Saraee , Faezeh Shekari , Ashraf Moini , Mehdi Mirzaei , Pooneh Ghaznavi , Shabnam Khodabakhshi , Anna Meyfour , Sara Fayazzadeh , Azadeh Ghaheri , Najmeh Salehi , Mohammad Reza Ghaffari , Ghasem Hosseini Salekdeh , Poopak Eftekhari Yazdi , Mehdi Totonchi

Research question

Can proteomic analysis of uterine fluid identify a panel of proteins that could potentially improve targeted embryo transfer strategies in IVF?

Design

Uterine fluid samples were collected from 18 patients who had undergone in vitro fertilization (IVF) with frozen embryo transfer 2 days before embryo transfer (11 patients in the main cohort and 7 patients in the independent cohort). Seven weeks later, patients were categorized into receptive and non-receptive groups based on ultrasonography results confirming clinical pregnancy. The proteins in these samples were analysed using tandem mass tag labelling and mass spectrometry. Differentially abundant proteins between the two groups were identified, and the candidate protein panel was selected based on the variable of importance in projection score and protein database analysis. The accuracy of the candidate panel was assessed using logistic regression, and findings were confirmed through western blot analysis.

Results

Bioinformatics analysis revealed that proteins related to protein synthesis, cell adhesion, keratinization, peroxisome proliferator-activated receptors, arachidonic acid metabolism and vascular endothelial growth factor were enriched in the receptive group. Biological processes, such as receptor internalization, negative regulation of cell junctions, the innate immune response, inflammatory response, and actin cytoskeleton organization were enriched in the non-receptive group. The key proteins, including desmoplakin, keratin type II cytoskeletal 1, the neuroblast differentiation-associated proteins AHNAK, moesin, and fibulin-1 were confirmed as potential biomarkers for assessing endometrial receptivity via western blot analysis.

Conclusion

The candidate panel may provide an approach for evaluating endometrial receptivity in the embryo transfer cycle, potentially improving personalized embryo transfer timing in clinical settings.

研究问题：子宫液的蛋白质组学分析能否确定一组可能潜在地改善体外受精中靶向胚胎移植策略的蛋白质？设计：收集胚胎移植前2天进行体外受精（IVF）冷冻胚胎移植的18例患者的子宫液样本（主队列11例，独立队列7例）。7周后，根据超声检查结果确定临床妊娠，将患者分为受胎组和未受胎组。这些样品中的蛋白质使用串联质量标记和质谱分析。鉴定两组间差异丰富的蛋白，根据投影评分的重要度变量和蛋白数据库分析选择候选蛋白面板。使用逻辑回归评估候选小组的准确性，并通过western blot分析证实结果。结果：生物信息学分析显示，受体组蛋白合成、细胞粘附、角化、过氧化物酶体增殖物激活受体、花生四烯酸代谢和血管内皮生长因子等相关蛋白富集。生物过程，如受体内化、细胞连接的负调节、先天免疫反应、炎症反应和肌动蛋白细胞骨架组织在非接受组中丰富。关键蛋白，包括desmoplakin、角蛋白II型细胞骨架1、神经母细胞分化相关蛋白AHNAK、moesin和纤维蛋白1，通过western blot分析被证实是评估子宫内膜容受性的潜在生物标志物。结论：候选小组可能为评估胚胎移植周期中的子宫内膜容受性提供一种方法，有可能改善临床环境中个性化的胚胎移植时机。

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引用次数: 0

Front Matter - Continued TOC 正面物质-继续TOC

IF 3.5 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Reproductive biomedicine online

Pub Date : 2025-12-01 DOI: 10.1016/S1472-6483(25)00590-5

引用次数: 0

Outside Back Cover - Editorial Board 封底外-编辑委员会

IF 3.5 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Reproductive biomedicine online

Pub Date : 2025-12-01 DOI: 10.1016/S1472-6483(25)00599-1

引用次数: 0

Inside Front Cover - Affiliations and First page of TOC 内部封面-附属机构和第一页的TOC

IF 3.5 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Reproductive biomedicine online

Pub Date : 2025-12-01 DOI: 10.1016/S1472-6483(25)00589-9

引用次数: 0

Factors influencing the rate of anti-Müllerian hormone decline: a retrospective study of 4245 infertile women 影响抗<s:1>勒氏激素下降率的因素：对4245名不孕妇女的回顾性研究。

IF 3.5 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Reproductive biomedicine online

Pub Date : 2025-12-01 DOI: 10.1016/j.rbmo.2025.105118

Shuxin Ma , Xuan Gao , Mengchun Hu , Nan Xie , Runxin Yao , Yaxuan Zhang , Junhao Yan , Yingying Qin , Peihao Liu

Research question

What factors influence the rate of decline in anti-Müllerian hormone (AMH) concentrations among infertile women?

Design

In this retrospective cohort, women who underwent repeated AMH measurements between January 2012 and December 2021 were enrolled. Participants were stratified into tertiles based on their annual AMH decline rate. Multivariable linear regression model was used to identify statistically significant predictors of AMH decline rates, adjusting for several potential confounders.

Results

In infertile women, key factors associated with an accelerated decline in AMH concentrations included more than three ovarian stimulation cycles (P = 0.030), tubal lesions (P < 0.001) and advanced baseline age (P < 0.001). Polycystic ovary syndrome (PCOS) was inversely associated with the rate of AMH decline (P < 0.001). No statistically significant associations were observed between AMH decline rates and ovulation induction, gynaecological surgery (ovarian or tubal), age at menarche, baseline AMH concentrations, baseline body mass index, education concentration or employment status in infertile women.

Conclusions

In infertile women, treatment for more than three ovarian stimulation cycles in assisted reproductive technology, tubal lesions and advanced age were factors associated with an accelerated rate of AMH decline, whereas PCOS was associated with a reduced rate of AMH decline. Medical intervention targeting these influencing factors may mitigate the rate of ovarian reserve loss and delay ovarian aging. The results specifically highlight the need for caution regarding the potential impairment of ovarian reserve due to repeated cycles of ovarian stimulation.

研究问题：什么因素影响不孕妇女抗勒氏激素（AMH）浓度下降的速度？设计：在这项回顾性队列研究中，纳入了2012年1月至2021年12月期间反复进行AMH测量的女性。参与者根据AMH的年下降率被分成几组。多变量线性回归模型用于确定AMH下降率的统计显著预测因子，调整了几个潜在的混杂因素。结果：在不孕妇女中，与AMH浓度加速下降相关的关键因素包括超过三个卵巢刺激周期（P = 0.030）、输卵管病变（P < 0.001）和基线年龄的提高（P < 0.001）。多囊卵巢综合征（PCOS）与AMH下降率呈负相关（P < 0.001）。不孕妇女AMH下降率与促排卵、妇科手术（卵巢或输卵管）、月经初潮年龄、基线AMH浓度、基线体重指数、教育程度或就业状况之间无统计学意义的关联。结论：在不孕妇女中，辅助生殖技术中超过三个卵巢刺激周期的治疗、输卵管病变和高龄是AMH下降速度加快的因素，而PCOS与AMH下降速度减慢有关。针对这些影响因素进行医学干预，可以减缓卵巢储备丧失的速度，延缓卵巢衰老。结果特别强调需要谨慎考虑卵巢储备的潜在损害，由于卵巢刺激的重复周期。

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引用次数: 0

Excessive KLF2 impairs mesenchymal–epithelial transition efficiency and adhesion in endometrial stromal cells via AKT phosphorylation 过量的KLF2通过AKT磷酸化影响子宫内膜间质-上皮细胞的转化效率和粘附。

IF 3.5 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Reproductive biomedicine online

Pub Date : 2025-12-01 DOI: 10.1016/j.rbmo.2025.105123

S. Yin , X. Liu , H. Zhao , X. Zhang , H. Bao

Research question

What is the dynamic expression profile of Krüppel-like factor 2 (KLF2) during the progression of mesenchymal–epithelial transition (MET), and through which molecular mechanisms does KLF2 regulate transformation?

Design

This study examined changes in KLF2 expression during the in-vivo menstrual cycle using immunohistochemistry and an in-vitro decidualization cell model. KLF2 negative control (KLF2-NC) and KLF2 overexpression (KLF2-OE) models were constructed in primary and immortalized human endometrial stromal cells via lentiviral transfection. Mesenchymal and epithelial protein changes were detected in the KLF2-NC and KLF2-OE groups on different days of MET using immunofluorescent staining. Potential KLF2 binding sites were predicted through motif enrichment analysis, and the interaction between KLF2 expression and AKT phosphorylation during MET was analysed using co-immunoprecipitation (co-IP) and western blotting. Finally, the effects of excessive KLF2 expression on the expression of adhesion factor and the efficiency of adhesion of BeWo-spheroids were determined.

Results

The results showed that KLF2 demonstrated significantly higher expression during the proliferative phase compared with the decidual phase in normal human endometrial tissue (P = 0.0095). Furthermore, KLF2 expression showed a progressive decline during MET. KLF2 overexpression decreased epithelial gene expression. Further, co-IP and western blotting demonstrated that KLF2 affects the MET process by regulating AKT phosphorylation, affecting the expression of adhesion factor and the efficiency of adhesion.

Conclusions

This study found that KLF2 expression changes during the menstrual cycle, and excessive KLF2 is not conducive to AKT phosphorylation during MET in the decidual phase.

研究问题：kr ppel样因子2 （KLF2）在间充质-上皮转化（MET）过程中的动态表达谱是什么？ KLF2通过哪些分子机制调控转化？设计：本研究使用免疫组织化学和体外脱胞细胞模型检测体内月经周期中KLF2表达的变化。通过慢病毒转染，在原代和永生化人子宫内膜基质细胞中构建KLF2阴性对照（KLF2- nc）和KLF2过表达（KLF2- oe）模型。免疫荧光染色法检测KLF2-NC组和KLF2-OE组在MET不同天数间充质和上皮蛋白的变化。通过基序富集分析预测潜在的KLF2结合位点，并使用共免疫沉淀（co-IP）和western blotting分析MET过程中KLF2表达与AKT磷酸化之间的相互作用。最后，测定KLF2过度表达对BeWo-spheroids粘附因子表达及粘附效率的影响。结果：正常人子宫内膜增殖期KLF2的表达明显高于蜕膜期（P = 0.0095）。此外，KLF2表达在MET期间呈进行性下降。KLF2过表达降低上皮基因表达。此外，co-IP和western blotting结果表明，KLF2通过调节AKT磷酸化影响MET过程，影响粘附因子的表达和粘附效率。结论：本研究发现KLF2在月经周期中表达发生变化，在蜕膜期MET时，KLF2过多不利于AKT磷酸化。

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引用次数: 0

Oestradiol and reproductive outcomes in ART: when too much of a good thing hurts 抗逆转录病毒治疗中的雌二醇和生殖结果：当好事太多会造成伤害时。

IF 3.5 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Reproductive biomedicine online

Pub Date : 2025-12-01 DOI: 10.1016/j.rbmo.2025.105131

Mathilde Bourdon , Chloé Maignien , Marion Ouazana , Fleur Kefelian , Louis Marcellin , Catherine Patrat , Khaled Pocate-Cheriet , Charles Chapron , Pietro Santulli

Oestradiol plays a crucial role in reproduction, particularly in assisted reproductive technology (ART), where it can reach supraphysiological concentrations. These fluctuations occur during ovarian stimulation in fresh embryo transfer cycles and during endometrial preparation for frozen embryo transfer, potentially impacting implantation and perinatal outcomes. Oestradiol influences endometrial proliferation, receptivity, implantation and placentation, with the sensitivity of the endometrium to systemic oestrogen emerging as a key determinant of reproductive success. In fresh embryo transfer cycles, ovarian stimulation induces histological, immunological and genetic changes in the endometrium, correlating with elevated oestradiol concentrations and possibly disrupting implantation. However, this adverse effect appears time-limited, as endometrial receptivity is restored in subsequent cycles. In FET cycles, both the duration and intensity of oestradiol exposure are critical, as excessive or prolonged exposure to exogenous oestradiol may impair reproductive outcomes. Despite these potential effects, strategies to regulate oestradiol concentrations in ART remain underexplored. This review examines the physiological and pathological roles of oestradiol in natural and ART cycles, emphasizing its impact on endometrial function, implantation and pregnancy outcomes. It highlights the need for further research to define optimal oestradiol thresholds and develop personalized ART protocols that consider both oestradiol concentrations and endometrial sensitivity to improve reproductive success and obstetric outcomes. Finally, it highlights strategies aimed at modulating oestradiol exposure to optimize reproductive success.

雌二醇在生殖中起着至关重要的作用，特别是在辅助生殖技术（ART）中，它可以达到超生理浓度。这些波动发生在新鲜胚胎移植周期的卵巢刺激和冷冻胚胎移植的子宫内膜准备期间，可能影响着床和围产期结局。雌二醇影响子宫内膜增殖、接受性、着床和胎盘，子宫内膜对全身雌激素的敏感性是生殖成功的关键决定因素。在新鲜胚胎移植周期中，卵巢刺激引起子宫内膜的组织学、免疫学和遗传变化，与雌二醇浓度升高相关，并可能破坏着床。然而，这种不良反应似乎是有时间限制的，因为子宫内膜容受性在随后的周期中恢复。在FET周期中，雌二醇暴露的持续时间和强度都是至关重要的，因为过度或长时间暴露于外源性雌二醇可能会损害生殖结果。尽管有这些潜在的影响，在抗逆转录病毒治疗中调节雌二醇浓度的策略仍未得到充分探索。本文综述了雌二醇在自然周期和ART周期中的生理和病理作用，重点介绍了其对子宫内膜功能、着床和妊娠结局的影响。它强调需要进一步研究，以确定最佳雌二醇阈值，并制定个性化的ART方案，同时考虑雌二醇浓度和子宫内膜敏感性，以提高生殖成功率和产科结果。最后，它强调了旨在调节雌二醇暴露以优化生殖成功的策略。

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引用次数: 0

Impact of native language on the pursuit of fertility care 母语对生育护理追求的影响。

IF 3.5 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Reproductive biomedicine online

Pub Date : 2025-12-01 DOI: 10.1016/j.rbmo.2025.105055

R. Garland Almquist, Marisa R. Young, Maranatha Genet, Heather Hipp

Research question

Are there any differences in the demographics, diagnostic work-up, fertility treatments attempted, and clinical pregnancy rate between patients whose native language is English compared with those whose native language is not English at a reproductive endocrinology and infertility (REI) clinic within an urban safety-net hospital in the USA?

Design

This retrospective cohort study included 321 patients who presented at the REI clinic between 2016 and 2022 with concern of infertility. The exposure of interest was native language spoken: English versus non-English. The primary outcome measure was attempt at any type of fertility treatment. Secondary outcome measures included completion of infertility diagnostic work-up, clinical pregnancy, and discontinuation of care.

Results

Among patients evaluated for infertility, 106 (33%) reported a native language other than English. Of 266 patients who underwent fertility testing, 218 (82%) completed sufficient diagnostic work-up to determine the type of infertility. Types of infertility were similar between the two groups, except for tubal factor infertility which was more common in native-English-speaking patients [62 (29%) versus 15 (14%); P = 0.003]. Fifty-six percent (149/266) of patients who underwent diagnostic testing for infertility attempted fertility treatment. Patients whose native language is not English were significantly more likely to attempt fertility treatment (adjusted risk ratio 1.44, 95% CI 1.09–1.91; P = 0.011) and to achieve clinical pregnancy (adjusted risk ratio 1.72, 95% CI 1.07–2.76; P = 0.025) compared with native-English-speaking patients. In total, 141 (44%) patients discontinued care.

Conclusions

Patients whose native language is not English were more likely to attempt fertility treatment and achieve clinical pregnancy compared with native-English-speaking patients. This suggests that, in a setting in the USA which aimed to reduce disparities and improve access to care, patients can overcome language barriers to pursue fertility care and undergo treatment.

研究问题：在美国城市安全网医院的生殖内分泌和不孕症（REI）诊所，母语为英语的患者与母语为非英语的患者在人口统计学、诊断检查、生育治疗尝试和临床妊娠率方面是否存在差异？设计：本回顾性队列研究纳入了2016年至2022年期间在REI诊所就诊的321例不孕患者。兴趣的暴露是母语口语：英语和非英语。主要结局指标是尝试任何类型的生育治疗。次要结局指标包括完成不孕症诊断检查、临床妊娠和终止治疗。结果：在评估为不孕症的患者中，106例（33%）报告母语非英语。在266例接受生育测试的患者中，218例（82%）完成了充分的诊断检查以确定不孕症的类型。两组之间的不孕症类型相似，除了输卵管因素不孕症在母语为英语的患者中更为常见[62（29%）对15 (14%)；P = 0.003]。56%（149/266）接受不孕症诊断测试的患者尝试过生育治疗。与母语为英语的患者相比，母语非英语的患者更有可能尝试生育治疗（调整风险比1.44,95% CI 1.09-1.91; P = 0.011）和实现临床妊娠（调整风险比1.72,95% CI 1.07-2.76; P = 0.025）。总共有141名（44%）患者停止了治疗。结论：与母语为英语的患者相比，母语为非英语的患者更有可能尝试生育治疗并实现临床妊娠。这表明，在旨在减少差异和改善护理机会的美国环境中，患者可以克服语言障碍，寻求生育护理并接受治疗。

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引用次数: 0

Towards a universal rapid warming protocol for cryopreserved human ovarian tissue 人类卵巢组织低温保存通用快速升温方案的研究。

IF 3.5 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Reproductive biomedicine online

Pub Date : 2025-12-01 DOI: 10.1016/j.rbmo.2025.105151

Cara Maria Färber , Rebekka Einenkel , Norah LA Emrich , Emily Zia Kestermann , Lodovico Parmegiani , Andreas Schallmoser , Nicole Sänger

Research question

Is it feasible to apply a universal warming protocol to slow-frozen human ovarian tissue, using the rapid-warming protocols already established for vitrified tissue, so that a single protocol could be used for both methods?

Design

Slow-frozen ovarian tissue samples from 25 patients were thawed by conventional protocol (slow freezing–thawing) or by a rapid-warming protocol produced ‘in-house’ or by commercially available media. Anti-Müllerian hormone values and follicular viability were determined before cryopreservation. Twenty-four hours after thawing, follicular viability was determined. Hypoxic tissue culture was conducted for 48 h to determine VEGF-A levels to estimate the angiogenic potential. Tissue sections were analysed with TUNEL staining for apoptosis and with haematoxylin and eosin staining for primordial follicles.

Results

Follicular survival did not statistically differ: based on fresh tissue (67.5), viable follicle numbers after conventional thawing (44.5), rapid warming with ‘in-house’ produced (54.5) and commercially available media (58.5) revealed no statistically significant differences between the groups, but were the highest using the rapid warming protocols. After 48 h in culture, preservation of primordial follicles was highest in the rapid warming groups (52% and 57%) compared with the regular thawing group (33%). No significant differences in vascular endothelial growth factor-A were observed comparing conventional thawing protocol with the rapid warming protocol using ‘in-house’-produced media. Although VEGF-A secretion was significantly lower in tissues after using commercially available rapid-warming media (P ≤ 0.0001) compared with conventional thawing, apoptosis level was significantly lower (P = 0.014) indicating improved tissue preservation.

Conclusions

Rapid-warming protocols provide similar to superior results compared with the conventional thawing approach. A universal protocol would increase the efficiency of ovarian tissue thawing–warming, potentially optimizing costs and improving outcome.

研究问题：使用已经建立的用于玻璃化组织的快速升温方案，将通用升温方案应用于慢速冷冻的人类卵巢组织是否可行，以便两种方法都可以使用单一方案？设计：25例患者缓慢冷冻的卵巢组织样本通过常规方案（缓慢冻融）或通过“内部”生产的快速升温方案或通过市售介质进行解冻。冷冻保存前测定抗勒氏杆菌激素值和卵泡活力。解冻后24小时，测定卵泡活力。组织缺氧培养48小时，测定VEGF-A水平，评估血管生成潜能。组织切片用TUNEL染色检测细胞凋亡，用苏木精和伊红染色检测原始卵泡。结果：卵泡存活率没有统计学差异：基于新鲜组织（67.5），常规解冻后的活卵泡数（44.5），用“内部”生产的快速加热（54.5）和市售培养基（58.5）显示各组之间没有统计学差异，但使用快速加热方案时最高。培养48 h后，快速加热组的原始卵泡保存率最高（52%和57%），而常规解冻组的保存率最高（33%）。血管内皮生长因子- a在常规解冻方案和使用“内部”生产培养基的快速升温方案之间没有显著差异。虽然与常规解冻相比，使用市售快速加热培养基后组织中VEGF-A的分泌显著降低（P≤0.0001），但细胞凋亡水平显著降低（P = 0.014），表明组织保存得到改善。结论：与传统的解冻方法相比，快速升温方案提供了类似的优越结果。一个通用的协议将提高卵巢组织解冻-升温的效率，潜在地优化成本和改善结果。

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引用次数: 0

Serum progesterone monitoring after embryo transfer. 胚胎移植后血清孕酮监测。

IF 3.5 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Reproductive biomedicine online

Pub Date : 2025-11-21 DOI: 10.1016/j.rbmo.2025.105412

Jan Tesarik

引用次数: 0

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