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In vivo gamete toxicology in the context of in vitro fertilization: a narrative review 体外受精背景下的体内配子毒理学:一个叙述性的回顾
Pub Date : 2025-06-01 Epub Date: 2025-03-27 DOI: 10.1016/j.xfnr.2025.100090
Morgan Orsolini M.S. , Jason Russack M.S. , Huey Huynh M.S. , Douglas Raburn Ph.D. , John Fox Ph.D. , Danny Schust M.D.
In vitro fertilization (IVF) as a clinical method to surmount infertility has existed since the 1970s, and yet fertilization, embryo development, pregnancy, and live birth rates remain unacceptably low. Although a multitude of factors may contribute to stagnated success despite substantial advances in basic and applied IVF sciences, gamete quality is inarguably integral to IVF treatment success rates. In this review, the investigators explored the role of environmental toxicology in impairing in vivo fertility and gamete quality before starting IVF, which may influence downstream IVF treatment success. In vivo, contaminants of interest that may affect gamete potential in the context of IVF treatment include heavy metals, perfluoroalkyl and polyfluoroalkyl substances, persistent organic pollutants, and airborne contaminants. This review aimed to provide clinicians with a comprehensive reference on potential toxicologic exposures by evaluating the existing literature on reproductive toxicology and the impact of toxic exposures on IVF clinical outcomes. It used in vitro and animal data to support correlational human studies with potential causative mechanisms and to emphasize the importance of patient evaluation of toxicologic risk.
自20世纪70年代以来,体外受精(IVF)作为一种克服不孕症的临床方法已经存在,但受精,胚胎发育,怀孕和活产率仍然低得令人无法接受。尽管试管婴儿基础和应用科学取得了长足的进步,但许多因素可能导致试管婴儿成功率停滞不前,配子质量无疑是试管婴儿治疗成功率不可或缺的一部分。在这篇综述中,研究人员探讨了环境毒理学在试管婴儿开始前损害体内生育能力和配子质量中的作用,这可能影响下游试管婴儿治疗的成功。在体内,在体外受精治疗中可能影响配子潜能的污染物包括重金属、全氟烷基和多氟烷基物质、持久性有机污染物和空气污染物。本综述旨在通过评估生殖毒理学的现有文献以及毒性暴露对体外受精临床结果的影响,为临床医生提供潜在毒理学暴露的综合参考。它使用体外和动物数据来支持与潜在致病机制相关的人类研究,并强调患者评估毒理学风险的重要性。
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引用次数: 0
Effectiveness of clinical touch, 2D, 3D, and 4D ultrasound guided embryo transfer: a systematic review and network meta-analysis of embryo transfer techniques 临床触摸、2D、3D和4D超声引导胚胎移植的有效性:胚胎移植技术的系统综述和网络荟萃分析
Pub Date : 2025-06-01 Epub Date: 2025-01-21 DOI: 10.1016/j.xfnr.2025.100088
Yusuf Beebeejaun M.R.C.O.G. , Timothy Copeland Ph.D. , Ippokratis Sarris D.M., F.R.C.O.G. , Marian Showell M.P.H. , Sesh K. Sunkara M.R.C.O.G. , James M.N. Duffy D.Phil.

Objective

With the use of two-dimensional ultrasound (2D US) in embryo transfer (ET) procedures now a widely accepted practice, and preferred over clinical touch (CT), there is growing interest in whether three-dimensional (3D) and four-dimensional (4D) US provide better outcomes for ET compared with traditional 2D methods. We aim to perform a network meta-analysis (NMA) to compare the clinical efficacy and safety of CT, 2D transabdominal (TAUS), 2D transvaginal (TVUS), 3D, and 4D US-guided ET.

Evidence Review

Randomized controlled trials (RCTs) indexed in PubMed, MEDLINE, EMBASE, clinical trial registries, and Cochrane Database of Systematic Reviews were searched from inception to December 2023. Identified RCTs were assessed for trustworthiness using the Trustworthiness in RAndomized Controlled Trials. Statistical analysis for pairwise was performed using Review Manager version 5.3 and NMAs were performed using STATA version 16. Random-effects modeling was used for data-pooling. Key outcomes included clinical pregnancy (CPRs) and live birth rates (LBRs), miscarriage rates, and ectopic pregnancy rates.

Results

Twenty-five RCTs of high integrity assessing 8,884 ET outcomes comparing CT, 2D TAUS-, 2D TVUS-, 3D TAUS-, and 4D TVUS-guided ET were included. The NMA identified lower LBR with CT (risk ratio [RR]: 0.78, 95% confidence interval [CI]: 0.59–1.03) compared with 2D TAUS. There were no significant differences in LBR between other methods, including 2D TVUS vs. 2D TAUS (RR: 1.03, 95% CI: 0.61–1.74), and 3D TAUS vs. 2D TAUS (RR: 1.01, 95% CI: 0.78–1.32). Clinical touch-guided ET was associated with a lower CPR compared with 2D TAUS (RR: 0.83, 95% CI: 0.75–0.91). There was no significant CPR difference comparing 2D TVUS vs. 2D (RR: 0.98, 95% CI: 0.83–1.16), 3D TAUS vs. 2D TAUS (RR 0.98, 95% CI: 0.80–1.20). Four-dimensional TVUS did not show a significant difference in either LBR or CPR compared with 2D TAUS, 3D TAUS, or CT.

Conclusion

For CPR, our study reinforces that ET guided by CT alone is inferior to 2D TAUS-guided transfer. However, when comparing 2D TAUS-, 2D TVUS-, 3D TAUS-, and 4D TVUS-guided ET, we found no evidence of significant differences in LBR, CPR, miscarriage rates, or ectopic pregnancy rates. The certainty of evidence for our primary outcome of CPR was rated as moderate, reflecting confidence in the results, but with notable concerns regarding study limitations and paucity of trials assessing the use of 3D and 4D US.
随着二维超声(2D US)在胚胎移植(ET)过程中的应用已被广泛接受,并且比临床触摸(CT)更受青睐,人们越来越关注三维(3D)和四维(4D)超声是否比传统的二维方法提供更好的ET结果。我们的目标是进行一项网络荟萃分析(NMA)来比较CT、2D经腹(TAUS)、2D经阴道(TVUS)、3D和4D us引导的et的临床疗效和安全性。证据综述检索PubMed、MEDLINE、EMBASE、临床试验注册库和Cochrane系统评价数据库中检索的随机对照试验(RCTs),从开始到2023年12月。使用随机对照试验中的可信度评估确定的随机对照试验的可信度。使用Review Manager 5.3版本进行两两统计分析,使用STATA 16版本进行nma。随机效应模型用于数据池。主要结局包括临床妊娠率(CPRs)和活产率(LBRs)、流产率和异位妊娠率。结果纳入25项高完整性随机对照试验,评估8,884个ET结果,比较CT、2D TAUS-、2D TVUS-、3D TAUS-和4D TVUS引导下的ET。与2D TAUS相比,NMA发现CT的LBR较低(风险比[RR]: 0.78, 95%可信区间[CI]: 0.59-1.03)。其他方法之间的LBR无显著差异,包括2D TVUS与2D TAUS (RR: 1.03, 95% CI: 0.61-1.74), 3D TAUS与2D TAUS (RR: 1.01, 95% CI: 0.78-1.32)。与2D TAUS相比,临床触摸引导下的ET与较低的CPR相关(RR: 0.83, 95% CI: 0.75-0.91)。2D tus与2D tus比较(RR: 0.98, 95% CI: 0.83-1.16), 3D TAUS与2D TAUS比较(RR 0.98, 95% CI: 0.80-1.20), CPR无显著差异。与2D TAUS、3D TAUS或CT相比,四维TVUS在LBR或CPR方面没有显着差异。结论对于心肺复苏术,我们的研究强调了CT单独引导下的ET转运不如二维tus引导下的转运。然而,当比较2D TAUS-、2D TVUS-、3D TAUS-和4D TVUS引导的ET时,我们发现LBR、CPR、流产率或异位妊娠率没有显著差异的证据。我们的CPR主要结局的证据确定性被评为中等,反映了对结果的信心,但值得注意的是研究的局限性和评估3D和4D US使用的试验的缺乏。
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引用次数: 0
The chromosomal challenge of human embryos: prevalence of aneuploidy and mosaicism 人类胚胎的染色体挑战:非整倍体和嵌合体的流行
Pub Date : 2025-06-01 Epub Date: 2024-11-16 DOI: 10.1016/j.xfnr.2024.100082
Ilya Volodyaev Ph.D. , Anna Ivanova M.Sc. , Elena Korchivaia M.Sc. , Alexey Surnov Ph.D. , Ekaterina Pomerantseva M.D., Ph.D. , Igor N. Lebedev M.D., Ph.D., Dr.Biol.Sc. , Maria L. Semenova Ph.D., Dr.Biol.Sc. , Ilya Mazunin Ph.D.
Chromosomal aberrations, such as whole-chromosome aneuploidies, segmental aneuploidies, whole-chromosome mosaicism, and segmental mosaicism, are key factors influencing embryonic development and the outcomes of fertility programs. This analytic review critically examines the prevalence and origins of these genetic abnormalities, emphasizing the significant maternal contribution to whole-chromosome aneuploidies and the age-related nature of these aberrations. In contrast, segmental aneuploidies, whole-chromosome mosaicism, and segmental mosaicism appear largely age-independent and show considerable variability across studies, mainly due to technical artifacts and methodological differences. By analyzing the accumulated data, scrutinizing methodological discrepancies in preimplantation genetic testing for aneuploidies, and distinguishing between biologic phenomena and artifacts, this review aims to clarify the current understanding of chromosomal aberrations in human embryos and their impact on reproductive health.
染色体畸变,如全染色体非整倍体、节段性非整倍体、全染色体嵌合体和节段嵌合体,是影响胚胎发育和生育计划结果的关键因素。这篇分析综述批判性地检查了这些遗传异常的患病率和起源,强调了母体对全染色体非整倍体的重要贡献以及这些异常的年龄相关性质。相反,片段性非整倍体、全染色体嵌合体和片段性嵌合体在很大程度上与年龄无关,并且在研究中表现出相当大的差异,主要是由于技术人工制品和方法差异。通过分析积累的数据,仔细检查非整倍体着床前遗传学检测的方法差异,区分生物现象和人工产物,本文旨在澄清目前对人类胚胎染色体畸变及其对生殖健康的影响的理解。
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引用次数: 0
Predicting the risk of ovarian hyperstimulation syndrome in women undergoing assisted reproductive technology treatments: a systematic review and quality assessment of prediction models 预测接受辅助生殖技术治疗的妇女卵巢过度刺激综合征的风险:预测模型的系统回顾和质量评估
Pub Date : 2025-06-01 Epub Date: 2025-01-03 DOI: 10.1016/j.xfnr.2024.100086
Krishnika Vetrivel M.B.B.S. , Ayesha Salejee M.B.B.S. , Bheena Kharunyam M.B.B.S. , Hakim-Moulay Dehbi Ph.D. , Spiros Denaxas Ph.D. , Nicholas Freemantle Ph.D. , Bassel H. Al Wattar Ph.D.

Importance

Ovarian hyperstimulation syndrome (OHSS) is a common iatrogenic complication of controlled ovarian stimulation (COS) in assisted conception. OHSS can be life-threatening and associated with significant morbidity. Several measures could help prevent OHSS; however, accurate risk prediction remains a challenge to enable early prevention.

Objective

To review available prediction models for OHSS in women undergoing assisted conception and to identify the best-performing models for their accuracy, generalizability, and applicability.

Evidence review

We searched electronic databases (MEDLINE, EMBASE, and CENTRAL) until October 2023. We included studies reporting on the development or evaluation of models predicting the risk of OHSS outcomes before or during COS among women undergoing assisted conception. We reported on models’ discrimination, calibration, type of validation, and any implementation tools for clinical practice.

Findings

We screened 5,699 citations and included 14 observational cohort studies reporting on 14 prediction models. The median sample size was 782 participants (range 105–256,381), and the majority of models were developed using logistic regression (13/14, 92.9%). The commonest predictor was maternal age (7/14, 50.0%), followed by number of antral and mature follicles (6/14, 42.9%). Six models were internally validated (6/14, 42.9%), and none were externally validated. Only one model had an implementation platform as a smartphone-based application (1/14, 7.1%). Most of the included studies had an unclear risk of bias (7/14, 50.0%), and only three studies were at low risk (3/13, 21.4%).

Conclusion and relevance

There are no clinically appropriate and validated prediction models for OHSS among women undergoing controlled ovarian stimulation. More research is needed to improve their generalizability and applicability into clinical practice.

PROSPERO

CRD42024509423
卵巢过度刺激综合征(OHSS)是辅助受孕控制性卵巢刺激(COS)常见的医源性并发症。OHSS可能危及生命,并伴有显著的发病率。有几项措施可以帮助预防OHSS;然而,准确的风险预测仍然是实现早期预防的一个挑战。目的回顾现有的辅助受孕女性OHSS预测模型,并从其准确性、普遍性和适用性方面确定最佳模型。我们检索了电子数据库(MEDLINE, EMBASE和CENTRAL),直到2023年10月。我们纳入了关于辅助受孕妇女COS前或COS期间OHSS风险预测模型开发或评估的研究报告。我们报告了模型的区分、校准、验证类型和任何临床实践的实施工具。研究结果:我们筛选了5699篇引用,纳入了14篇观察性队列研究,报告了14个预测模型。中位样本量为782名参与者(范围105-256,381),大多数模型采用逻辑回归(13/14,92.9%)。最常见的预测因子是母亲年龄(7/14,50.0%),其次是窦泡和成熟卵泡数量(6/14,42.9%)。6个模型被内部验证(6/14,42.9%),没有模型被外部验证。只有一个模型具有基于智能手机的应用程序的实现平台(1/14,7.1%)。大多数纳入的研究偏倚风险不明确(7/14,50.0%),只有3项研究为低风险(3/13,21.4%)。结论及相关性对于接受卵巢控制性刺激的女性,尚无临床合适且有效的预测模型。需要更多的研究来提高它们在临床实践中的普遍性和适用性。PROSPEROCRD42024509423
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引用次数: 0
Prevalence of adenomyosis in symptomatic adolescents and young women: a systematic review and meta-analysis 有症状的青少年和年轻女性的子宫腺肌症患病率:一项系统回顾和荟萃分析
Pub Date : 2025-06-01 Epub Date: 2024-12-03 DOI: 10.1016/j.xfnr.2024.100083
Paolo Vercellini M.D. , Camilla Buffo R.M. , Veronica Bandini M.D. , Sonia Cipriani Sc.D. , Francesca Chiaffarino M.Sc. , Paola Viganò Ph.D. , Edgardo Somigliana M.D., Ph.D.
<div><h3>Objective</h3><div>Many adolescents and young women experience dysmenorrhea, a condition that is often trivialized or overlooked but can cause a substantial deterioration in health-related quality of life. Therefore, we conducted a systematic review and meta-analysis to investigate the overall prevalence of symptomatic individuals with ultrasound/magnetic resonance imaging–diagnosed adenomyosis in the 12–25 year-age group. This could inform management and treatment decisions.</div></div><div><h3>Evidence Review</h3><div>The PubMed/Medline, Embase, and Scopus databases were searched for full-length, English-language reports published between 2015 and 2024. This systematic review with meta-analysis was conducted and reported following the Joanna Briggs Institute methodological guidance for systematic reviews of observational epidemiological studies reporting prevalence and cumulative incidence data. We included observational studies that assessed the number of patients with adenomyosis among adolescents and young women, the majority of whom presented with dysmenorrhea. The methodological quality of the included studies and their potential risk of bias were ascertained using the Joanna Briggs Institute Critical Appraisal Tool for Prevalence Studies. The main outcome was the prevalence of adenomyosis among symptomatic adolescents (midpoint of the study age range, <20 years) and young women (midpoint of the study age range, ≥20 years). Three meta-analyses, categorized by age, were performed using Stata to pool adenomyosis prevalence data from selected studies. The risk of endometriosis in women with and without adenomyosis was ultimately assessed as an exploratory and confirmatory investigation by combining the odds ratio estimates from each study using the random-effects model.</div></div><div><h3>Results</h3><div>Six studies comprising 1,300 individuals met the inclusion criteria. The prevalence of adenomyosis ranged from 5.9% to 46.0%, with an overall weighted mean of 20.7% (95% confidence interval [CI], 11.5–31.6) with high heterogeneity (<em>I</em><sup><em>2</em></sup> = 94.8%). The aggregate estimates were as 16.9% (95% CI, 8.8%–27.0%) in the adolescent subgroup and 29.7% (95% CI, 17.5%–43.5%) in the young woman subgroup. The risk of endometriosis in patients with adenomyosis was significantly higher than that in patients without adenomyosis, with a pooled odds ratio of 3.39 (95% CI, 2.11–5.45), without statistically significant heterogeneity across studies.</div></div><div><h3>Conclusion</h3><div>The findings of the present review should assist clinicians in developing a high index of suspicion for adenomyosis when adolescents and young women present with chronic severe dysmenorrhea and menorrhagia. Limiting the diagnostic delay and considering secondary prevention medical interventions may improve the quality of life and limit the risk of disease progression. Further rigorous prospective analytic studies are required to better defi
许多青少年和年轻妇女经历痛经,这种情况往往被忽视或忽视,但可能导致健康相关生活质量的严重恶化。因此,我们进行了一项系统回顾和荟萃分析,以调查12-25岁年龄组中超声/磁共振成像诊断为子宫腺肌症的症状个体的总体患病率。这可以为管理和治疗决策提供信息。在PubMed/Medline、Embase和Scopus数据库中检索2015年至2024年间发表的完整的英文报告。采用荟萃分析的系统评价是按照乔安娜布里格斯研究所的方法指导进行的,该方法指导对报告患病率和累积发病率数据的观察性流行病学研究进行系统评价。我们纳入了观察性研究,评估了青少年和年轻女性中子宫腺肌症患者的数量,其中大多数患者表现为痛经。采用乔安娜布里格斯研究所流行病学研究关键评估工具确定纳入研究的方法学质量及其潜在的偏倚风险。主要结局是有症状的青少年(研究年龄范围的中点,20岁)和年轻女性(研究年龄范围的中点,≥20岁)中子宫腺肌症的患病率。使用Stata进行了三项按年龄分类的荟萃分析,以汇总来自选定研究的子宫腺肌症患病率数据。通过使用随机效应模型结合各研究的优势比估计,最终对患有和不患有子宫腺肌症的女性子宫内膜异位症的风险进行了探索性和确证性调查。结果6项研究共纳入1300名受试者,符合纳入标准。子宫腺肌症患病率为5.9% ~ 46.0%,总体加权平均值为20.7%(95%可信区间[CI], 11.5 ~ 31.6),异质性高(I2 = 94.8%)。青少年亚组的总估计值为16.9% (95% CI, 8.8%-27.0%),年轻女性亚组为29.7% (95% CI, 17.5%-43.5%)。子宫腺肌症患者发生子宫内膜异位症的风险显著高于无子宫腺肌症患者,合并优势比为3.39 (95% CI, 2.11-5.45),各研究间无统计学意义的异质性。结论本综述的发现应有助于临床医生在青少年和年轻女性慢性严重痛经和月经过多时对子宫腺肌症的高度怀疑。限制诊断延迟并考虑二级预防医疗干预可以改善生活质量并限制疾病进展的风险。需要进一步严格的前瞻性分析研究,以更好地确定月经后十年不同人群亚群中子宫腺肌症的流行病学模式。
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引用次数: 0
Promises and pitfalls of preimplantation genetic testing for polygenic disorders: a narrative review 多基因疾病胚胎植入前基因检测的前景和缺陷:叙述性回顾
Pub Date : 2025-06-01 Epub Date: 2024-12-19 DOI: 10.1016/j.xfnr.2024.100085
Jaime A. Roura-Monllor M.D., M.S. , Zachary Walker M.D. , Joel M. Reynolds Ph.D. , Greysha Rivera-Cruz M.D. , Avner Hershlag M.D. , Gheona Altarescu M.D. , Sigal Klipstein M.D. , Stacey Pereira Ph.D. , Gabriel Lázaro-Muñoz Ph.D., J.D. , Shai Carmi Ph.D. , Todd Lencz Ph.D. , Ruth Bunker Lathi M.D.
Preimplantation genetic testing for polygenic disorders (PGT-P) has been commercially available since 2019. Preimplantation genetic testing for polygenic disorders makes use of polygenic risk scores for conditions that are multifactorial and are significantly influenced by environmental and lifestyle factors. If current predictions are accurate, then absolute risk reductions range from approximately 0.02% to 10.1%, meaning that between 10 and 5,000 in vitro fertilization patients would need to be tested with PGT-P to prevent 1 offspring from becoming affected in the future, depending on the condition and the number of embryos available. Survey and interview data reveal that patients and the public have largely favorable views regarding the use of PGT-P for disease prevention; however, clinicians and professional organizations have many reservations. The use of PGT-P raises multiple social and ethical concerns including the need for adequate counseling, the setting of realistic expectations, the application of distributive justice, the impact of environmental and social determinants of health, and the potential exacerbation of health inequities. Clinicians expressed significant concerns relating to the cost of PGT-P, the potential time-consuming counseling for reproductive endocrinologists and genetic counselors, the intentional creation of supernumerary embryos, and patients’ unrealistic expectations regarding “healthiest disease-free” embryos. Furthermore, current evidence lacks long-term outcome data and generalizability. Before offering PGT-P to patients, additional clinical validation studies are needed. Also, ethical and social considerations raised by PGT-P should be carefully delineated. Systemic practices to increase equitable access to unbiased genetic counseling and reproductive services would be desirable before the ethical implementation of PGT-P.
自2019年以来,多基因疾病的植入前基因检测(PGT-P)已经商业化。多基因疾病的植入前基因检测使用多基因风险评分,用于多因素且受环境和生活方式因素显著影响的疾病。如果目前的预测是准确的,那么绝对风险降低范围约为0.02%至10.1%,这意味着10至5000名体外受精患者将需要接受PGT-P测试,以防止未来有1名后代受到影响,具体取决于条件和可用胚胎的数量。调查和访谈数据显示,患者和公众对使用PGT-P进行疾病预防有很大的好感;然而,临床医生和专业组织有许多保留意见。PGT-P的使用引起了多重社会和伦理关切,包括需要适当的咨询、设定现实的期望、实行分配正义、环境和社会决定因素对健康的影响以及卫生不平等的潜在加剧。临床医生对PGT-P的成本、对生殖内分泌学家和遗传咨询师潜在的耗时咨询、故意制造多余胚胎以及患者对“最健康无病”胚胎的不切实际的期望表示了极大的关注。此外,目前的证据缺乏长期结果数据和普遍性。在向患者提供PGT-P之前,需要进行额外的临床验证研究。此外,PGT-P提出的伦理和社会方面的考虑应该仔细描述。在伦理上实施PGT-P之前,增加公平获得公正的遗传咨询和生殖服务的系统实践是可取的。
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引用次数: 0
Epithelial-mesenchymal transition links inflammation and fibrosis in the pathogenesis of endometriosis: a narrative review 在子宫内膜异位症的发病机制中,上皮-间质转化与炎症和纤维化有关:一个叙述性的回顾
Pub Date : 2025-06-01 Epub Date: 2025-02-15 DOI: 10.1016/j.xfnr.2025.100089
Zoé I. Vincent-Mistiaen Ph.D.
Endometriosis, a chronic inflammatory condition, is characterized by the growth of endometrial-like tissue outside the uterus, leading to debilitating pain and infertility. Although retrograde menstruation is widely accepted as a mechanism for the dissemination of endometrial cells to ectopic sites, the processes that enable their survival, invasion, and lesion formation remain incompletely understood. Epithelial-mesenchymal transition (EMT) has emerged as a potential driver, promoting cellular plasticity that supports ectopic implantation and invasion. Epithelial-mesenchymal transition is closely linked to inflammation, with transforming growth factor-β–mediated pathways playing a central role in driving these transitions. Chronic inflammation also induces fibroblast-myofibroblast transition (FMT) and smooth muscle metaplasia, processes that exacerbate fibrosis through excessive extracellular matrix deposition and fibroblast activation. These fibrotic changes worsen symptoms and contribute to disease progression. This review explores EMT and FMT as key mechanistic links between inflammation and fibrosis and discusses how targeting these pathways could offer novel therapeutic strategies to disrupt fibrotic progression, alleviate symptoms, and improve patient outcomes. Additionally, EMT and FMT markers hold promise as diagnostic tools, offering potential for earlier detection and more precise staging of endometriosis.
子宫内膜异位症是一种慢性炎症,其特征是子宫外子宫内膜样组织的生长,导致虚弱的疼痛和不孕。尽管逆行月经被广泛认为是子宫内膜细胞向异位部位扩散的一种机制,但使其存活、侵袭和病变形成的过程仍不完全清楚。上皮-间质转化(Epithelial-mesenchymal transition, EMT)已成为一个潜在的驱动因素,促进细胞可塑性,支持异位植入和侵袭。上皮-间质转变与炎症密切相关,转化生长因子-β介导的途径在驱动这些转变中起着核心作用。慢性炎症还会诱导成纤维细胞-肌成纤维细胞转化(FMT)和平滑肌化生,这些过程通过过度的细胞外基质沉积和成纤维细胞活化而加剧纤维化。这些纤维化改变使症状恶化并促进疾病进展。这篇综述探讨了EMT和FMT作为炎症和纤维化之间的关键机制联系,并讨论了如何靶向这些途径可以提供新的治疗策略来破坏纤维化进展,缓解症状,改善患者预后。此外,EMT和FMT标记物有望作为诊断工具,为子宫内膜异位症的早期检测和更精确的分期提供潜力。
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引用次数: 0
The role of alpha-Klotho protein in male and female reproduction. A systematic review α - klotho蛋白在雌雄生殖中的作用。系统回顾
Pub Date : 2025-06-01 Epub Date: 2024-12-04 DOI: 10.1016/j.xfnr.2024.100084
Noemie Sachs-Guedj M.D. , Piotr Sokol M.D. , Tania Quesada-López Ph.D. , Thomas Freour Pharm.D., Ph.D. , Nikolaos P. Polyzos Ph.D. , Francisca Martinez Ph.D.

Objective

The aim of this systematic review is to provide the first comprehensive overview of the current knowledge regarding the role of the alpha-Klotho protein in male and female fertility, focusing on the testicle, spermatozoa, ovary, and oocyte.

Evidence Review

A comprehensive literature search was conducted up to March 2024 to determine the role of Klotho (KL, alpha-Klotho) in human reproductive tissues. The search terms included the following: “Klotho” AND “Sperm” OR “Testicle” OR “Oocyte” OR “Ovary” OR “Reproduction” OR “Fertility” OR “Infertility” OR “Gamete” OR “Gonad.” Following Cochrane methodology, the search covered MEDLINE, EMBASE, Cochrane Library, National Center for Biotechnology Information Gene, Tabula Sapiens, GTEx, Trip Database, Google Scholar, medRxiv, Open Grey, Central Register of Controlled Trials, and World Health Organization International Clinical Trials Registry, including all relevant studies up to March 2024 without language or publication status restrictions. The focus was on the role of alpha-Klotho in fertility, including studies involving animals and humans and basic experimental or observational designs. After removing duplicates, 2 investigators (N.S-.G., F.M.) independently screened titles and abstracts, with disagreements resolved by a third investigator (P.S.). The search identified a total of 258 articles, of which 18 were selected for the review. Final eligibility was determined by 4 investigators (N.S-.G., P.S., T.Q-.L., F.M.).

Results

The Klotho protein levels decrease with age. This decline influences male fertility by impacting spermatogenesis, sperm maturation, androgen production, and local homeostasis. In women, KL influences ovulatory function by inhibiting hypothalamic gonadotropin-releasing hormone secretion, regulating growth hormone secretion and oocyte quality, and controlling granulosa cells and follicular apoptosis. Overall, animal and human studies indicate that Klotho is an important factor in fertility, contributing to sperm quality and oocyte maturation and development. Additionally, the antioxidant properties of KL may help preserve the integrity of sperm cells and could serve as an effective antioxidant for the cryopreservation of ovarian tissue.

Conclusion

Further research is warranted to fully understand the mechanisms underlying the role of KL protein in human fertility, both as a potential biomarker and as a therapeutic target for infertility treatments and fertility preservation strategies. Advances in functional genetic variations studies will clarify the pathways linking genotype to phenotype in reproductive health.
目的:本系统综述的目的是提供关于α - klotho蛋白在男性和女性生育能力中的作用的最新知识,重点是睾丸、精子、卵巢和卵母细胞。为了确定Klotho (KL, alpha-Klotho)在人类生殖组织中的作用,我们进行了截至2024年3月的全面文献检索。搜索词包括:“克洛索”、“精子”、“睾丸”、“卵母细胞”、“卵巢”、“生殖”、“生育能力”、“不育”、“配子”、“性腺”。按照Cochrane的方法,检索涵盖MEDLINE、EMBASE、Cochrane图书馆、国家生物技术信息基因中心、Tabula Sapiens、GTEx、Trip Database、谷歌Scholar、medRxiv、Open Grey、Central Register of Controlled Trials和World Health Organization International Clinical Trials Registry,包括截至2024年3月的所有相关研究,没有语言或出版状态限制。重点是alpha-Klotho在生育方面的作用,包括涉及动物和人类的研究以及基本的实验或观察设计。在去除重复项后,2名调查人员(n.s. - g.g。, F.M.)独立筛选标题和摘要,分歧由第三方研究者解决(P.S.)。检索共发现258篇文章,其中18篇入选综述。最终入选资格由4名研究者(n.s. - g.g)决定。, p.s., t.q - l。F.M.)。结果Klotho蛋白水平随年龄增长而降低。这种下降通过影响精子发生、精子成熟、雄激素产生和局部稳态来影响男性生育能力。在女性中,KL通过抑制下丘脑促性腺激素释放激素分泌、调节生长激素分泌和卵母细胞质量、控制颗粒细胞和卵泡凋亡来影响排卵功能。总的来说,动物和人体研究表明,Klotho是生育能力的重要因素,有助于精子质量和卵母细胞的成熟和发育。此外,KL的抗氧化特性可能有助于保持精子细胞的完整性,并可作为卵巢组织冷冻保存的有效抗氧化剂。结论KL蛋白在人类生育中的作用机制有待进一步研究,无论是作为潜在的生物标志物,还是作为不孕症治疗和生育保护策略的治疗靶点。功能遗传变异研究的进展将阐明生殖健康中基因型与表型的联系途径。
{"title":"The role of alpha-Klotho protein in male and female reproduction. A systematic review","authors":"Noemie Sachs-Guedj M.D. ,&nbsp;Piotr Sokol M.D. ,&nbsp;Tania Quesada-López Ph.D. ,&nbsp;Thomas Freour Pharm.D., Ph.D. ,&nbsp;Nikolaos P. Polyzos Ph.D. ,&nbsp;Francisca Martinez Ph.D.","doi":"10.1016/j.xfnr.2024.100084","DOIUrl":"10.1016/j.xfnr.2024.100084","url":null,"abstract":"<div><h3>Objective</h3><div>The aim of this systematic review is to provide the first comprehensive overview of the current knowledge regarding the role of the alpha-Klotho protein in male and female fertility, focusing on the testicle, spermatozoa, ovary, and oocyte.</div></div><div><h3>Evidence Review</h3><div>A comprehensive literature search was conducted up to March 2024 to determine the role of Klotho (KL, alpha-Klotho) in human reproductive tissues. The search terms included the following: “Klotho” AND “Sperm” OR “Testicle” OR “Oocyte” OR “Ovary” OR “Reproduction” OR “Fertility” OR “Infertility” OR “Gamete” OR “Gonad.” Following Cochrane methodology, the search covered MEDLINE, EMBASE, Cochrane Library, National Center for Biotechnology Information Gene, Tabula Sapiens, GTEx, Trip Database, Google Scholar, medRxiv, Open Grey, Central Register of Controlled Trials, and World Health Organization International Clinical Trials Registry, including all relevant studies up to March 2024 without language or publication status restrictions. The focus was on the role of alpha-Klotho in fertility, including studies involving animals and humans and basic experimental or observational designs. After removing duplicates, 2 investigators (N.S-.G., F.M.) independently screened titles and abstracts, with disagreements resolved by a third investigator (P.S.). The search identified a total of 258 articles, of which 18 were selected for the review. Final eligibility was determined by 4 investigators (N.S-.G., P.S., T.Q-.L., F.M.).</div></div><div><h3>Results</h3><div>The Klotho protein levels decrease with age. This decline influences male fertility by impacting spermatogenesis, sperm maturation, androgen production, and local homeostasis. In women, KL influences ovulatory function by inhibiting hypothalamic gonadotropin-releasing hormone secretion, regulating growth hormone secretion and oocyte quality, and controlling granulosa cells and follicular apoptosis. Overall, animal and human studies indicate that Klotho is an important factor in fertility, contributing to sperm quality and oocyte maturation and development. Additionally, the antioxidant properties of KL may help preserve the integrity of sperm cells and could serve as an effective antioxidant for the cryopreservation of ovarian tissue.</div></div><div><h3>Conclusion</h3><div>Further research is warranted to fully understand the mechanisms underlying the role of KL protein in human fertility, both as a potential biomarker and as a therapeutic target for infertility treatments and fertility preservation strategies. Advances in functional genetic variations studies will clarify the pathways linking genotype to phenotype in reproductive health.</div></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":"6 1","pages":"Article 100084"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143134271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Fertoprotective agents and tumor response: a narrative review 铁保护剂和肿瘤反应:一个叙述性的回顾
Pub Date : 2025-06-01 Epub Date: 2025-01-21 DOI: 10.1016/j.xfnr.2025.100087
Addison W. Alley M.D. , Jonathan E. Constance Ph.D. , Joseph M. Letourneau M.D.
As advances in cancer therapy have significantly improved mortality rates, there is increasing emphasis on improving quality of life for cancer survivors. One such area of focus is in maintaining fertility, as both chemotherapy and radiation therapy carry significant risks of causing infertility through various mechanisms of gonadal injury. Although fertility preservation options exist, such as sperm or egg banking, they are not always available or indicated for all patients. Fertoprotective agents are proposed substances that may serve to protect the gonad from the harmful impacts of cancer therapy to maintain fertility. However, caution must be taken to evaluate whether these agents could act similarly to protect the tumor from anticancer therapies. In this narrative review, we first describe the various mechanisms by which chemotherapy or radiation therapy can cause gonadal harm. We then review the available research on fertoprotective agents and their proposed mechanisms of gonadal protection. Finally, we discuss what evidence exists for interaction with cancer therapy for each agent, with an emphasis on opportunities for future research.
随着癌症治疗的进步大大降低了死亡率,人们越来越重视提高癌症幸存者的生活质量。其中一个重点领域是维持生育能力,因为化疗和放疗都有通过各种性腺损伤机制导致不孕的重大风险。尽管存在保留生育能力的选择,如精子或卵子银行,但它们并不总是可用或适用于所有患者。卵泡保护剂是一种被提出的物质,可以保护性腺免受癌症治疗的有害影响,以保持生育能力。然而,必须谨慎评估这些药物是否能起到类似的保护肿瘤免受抗癌治疗的作用。在这篇叙述性综述中,我们首先描述了化疗或放疗可能导致性腺损害的各种机制。然后,我们回顾了现有的研究对生殖保护剂和他们提出的性腺保护机制。最后,我们讨论了每种药物与癌症治疗相互作用的证据,并强调了未来研究的机会。
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引用次数: 0
Polycystic ovary syndrome and miscarriage: a narrative review 多囊卵巢综合征与流产:叙述性综述
Pub Date : 2024-10-01 Epub Date: 2024-08-13 DOI: 10.1016/j.xfnr.2024.100078
Leeann M. Bui M.D. , Lusine Aghajanova M.D., P.h.D. , Ruth B. Lathi M.D. , Anna Sokalska M.D., Ph.D.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age. Although women with PCOS are often identified when presenting for oligomenorrhea or infertility care, PCOS is also linked to several metabolic morbidities, which may predispose to poor reproductive outcomes. Research has also suggested a possible independent association between PCOS and miscarriage, although available data are conflicting. This review focuses on the current literature regarding the risk of miscarriage and recurrent pregnancy loss in women with PCOS. First, we give an overview of the prevalence of miscarriage and recurrent pregnancy loss in this population and identify study limitations that contribute to the conflicting data regarding the potential association. Subsequently, we review the current literature on obesity, insulin resistance and hyperinsulinemia, thrombophilia, hyperandrogenism, oocyte, and embryo quality and viability, endometrial receptivity, oxidative stress and chronic inflammation, in addition to the efficacy of potential risk-mitigating interventions for miscarriage in women with PCOS.

多囊卵巢综合征(PCOS)是影响育龄妇女最常见的内分泌疾病。虽然患有多囊卵巢综合症的女性通常是在出现月经量少或不孕症时被发现的,但多囊卵巢综合症还与多种代谢性疾病有关,这些疾病可能导致不良的生殖结果。研究还表明,多囊卵巢综合症与流产之间可能存在独立的关联,但现有数据并不一致。本综述重点关注有关多囊卵巢综合症女性流产和复发性妊娠失败风险的现有文献。首先,我们概述了这一人群中流产和复发性妊娠失败的发生率,并指出了研究的局限性,这些局限性导致了有关潜在关联的数据相互矛盾。随后,我们回顾了有关肥胖、胰岛素抵抗和高胰岛素血症、血栓性疾病、高雄激素、卵母细胞和胚胎质量及存活率、子宫内膜接受能力、氧化应激和慢性炎症的现有文献,以及针对多囊卵巢综合征妇女流产的潜在风险缓解干预措施的有效性。
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引用次数: 0
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