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The evidence-practice gap in immunotherapy for recurrent pregnancy loss: a critical narrative review of current treatments 免疫疗法治疗复发性妊娠丢失的证据与实践差距:对当前治疗方法的批判性述评
Pub Date : 2025-10-15 DOI: 10.1016/j.xfnr.2025.100099
Ida Behrendt Møller M.D. , Kilian Vomstein Dr. med. habil. , Maria Christine Krog Ph.D. , Ruth Bunker Lathi Ph.D. , Henriette Svarre Nielsen D.M.Sc
Many clinicians suspect immune problems when treating women with unexplained recurrent pregnancy loss (RPL); however, we lack evidence that immunotherapy helps. Although immune tolerance is crucial for successful pregnancy, distinguishing immunologic from nonimmunologic causes of RPL continues to be a major hurdle. Apart from antiphospholipid syndrome (APS), decades of studying immune markers have yielded no reliable diagnostic tests. This diagnostic uncertainty has led to widespread off-label use of immunomodulatory treatments without strong evidence of a positive effect on pregnancy outcomes. This review examines current data on frequently used immune therapies including corticosteroids, intravenous immunoglobulin, lymphocyte immunotherapy, calcineurin inhibitors, anticoagulants, and granulocyte colony–stimulating factor. Small studies with diverse demographics and contradictory findings make up most of the information available. There are only a few high-quality randomized controlled trials, frequently demonstrating no significant treatment benefit. Designing such trials is particularly challenging because of the heterogeneous nature of RPL, which may involve patients with genetic, anatomical, endocrine, and immunologic risk factors. Ideally, such trials only include patients with similar underlying pathologies to generate robust and reliable evidence. Current evidence does not support routine use of these expensive and potentially dangerous therapies. Future progress requires identifying trustworthy biomarkers that can distinguish immune-mediated RPL from other causes to identify women who potentially could benefit from immune modulation and conducting appropriately powered randomized controlled trials in well-defined patient populations.
许多临床医生在治疗不明原因复发性妊娠丢失(RPL)的妇女时怀疑免疫问题;然而,我们缺乏免疫疗法有帮助的证据。尽管免疫耐受对妊娠成功至关重要,但区分RPL的免疫与非免疫原因仍然是一个主要障碍。除了抗磷脂综合征(APS)外,几十年来对免疫标记物的研究还没有产生可靠的诊断测试。这种诊断的不确定性导致在没有强有力证据表明对妊娠结局有积极影响的情况下广泛使用免疫调节治疗。本文综述了目前常用的免疫疗法的数据,包括皮质类固醇、静脉注射免疫球蛋白、淋巴细胞免疫疗法、钙调磷酸酶抑制剂、抗凝血剂和粒细胞集落刺激因子。具有不同人口统计数据和相互矛盾的结果的小型研究构成了大部分可用的信息。只有少数高质量的随机对照试验,经常显示没有显著的治疗效果。设计这样的试验尤其具有挑战性,因为RPL的异质性,可能涉及患者的遗传、解剖、内分泌和免疫风险因素。理想情况下,这样的试验只包括具有相似基础病理的患者,以产生强有力和可靠的证据。目前的证据不支持常规使用这些昂贵且有潜在危险的疗法。未来的进展需要确定可信赖的生物标志物,将免疫介导的RPL与其他原因区分开来,以确定可能从免疫调节中受益的妇女,并在明确的患者群体中进行适当的随机对照试验。
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引用次数: 0
The role of somatic mutations in endometriosis: pathogenesis, progression, and fibrogenesis (narrative review) 体细胞突变在子宫内膜异位症中的作用:发病机制、进展和纤维形成(叙述性综述)
Pub Date : 2025-10-09 DOI: 10.1016/j.xfnr.2025.100098
Leila Adamyan Ph.D. , Laura Pivazyan M.D. , Maria Yurkanova M.D. , Evdokiya Zarova M.D. , Maria Kuznetsova Ph.D. , Karina Mailova Ph.D. , Dmitry Trofimov Ph.D. , Assia Stepanian Ph.D.
Endometriosis is a common gynecological disorder affecting 10% of reproductive-aged women, characterized by ectopic endometrial-like tissue exhibiting malignant-like behaviors including invasiveness and angiogenesis. Growing evidence identifies recurrent somatic mutations in cancer driver genes (KRAS, ARID1A, PIK3CA, and PTEN) within endometriotic lesions, suggesting their potential role in disease pathogenesis. This narrative review examines the contribution of somatic mutations to endometriosis development and fibrogenesis, their biomarker potential, and therapeutic implications. We conducted a comprehensive literature search (PubMed, Scopus, and Cochrane, encompassing all publications from the earliest available records of each database up to May 2025) focusing on next-generation sequencing–based studies of endometriotic lesions, particularly analyzing fibrotic remodeling and oxidative stress mechanisms.
Analysis of 15 key studies revealed the following: somatic mutations across all lesion subtypes (ovarian, deep infiltrating, and peritoneal); oxidative stress from retrograde menstruation and iron overload as likely mutagenic drivers promoting fibrogenesis; distinct mutational patterns between epithelial and stromal components indicating oligoclonal origins; and lesion-specific mutation profiles within individual patients suggesting independent clonal evolution. Notably, although these mutations mirror those in cancers, endometriosis typically remains benign, implying microenvironmental constraints on malignant transformation.
Somatic mutations appear actively involved in endometriosis pathogenesis and fibrogenesis rather than being incidental findings. Their detection in benign lesions underscores the disease’s molecular complexity. Further research should focus on mutation-microenvironment interactions to develop molecular classifications and targeted therapies, potentially revolutionizing endometriosis management through personalized approaches.
子宫内膜异位症是一种常见的妇科疾病,影响10%的育龄妇女,其特征是子宫内膜样组织异位,表现出恶性样行为,包括侵袭性和血管生成。越来越多的证据表明,子宫内膜异位症病变中癌症驱动基因(KRAS, ARID1A, PIK3CA和PTEN)的复发性体细胞突变表明它们在疾病发病机制中的潜在作用。本文综述了体细胞突变对子宫内膜异位症发展和纤维形成的影响,以及它们的生物标志物潜力和治疗意义。我们进行了全面的文献检索(PubMed, Scopus和Cochrane,包括每个数据库中最早的可用记录到2025年5月的所有出版物),重点是基于下一代子宫内膜异位症病变测序的研究,特别是分析纤维化重塑和氧化应激机制。对15项关键研究的分析显示:所有病变亚型(卵巢、深部浸润和腹膜)的体细胞突变;月经逆行引起的氧化应激和铁超载可能是促进纤维形成的致突变驱动因素;上皮和基质成分之间的不同突变模式表明寡克隆起源;个别患者的病变特异性突变谱表明独立的克隆进化。值得注意的是,尽管这些突变反映了癌症,子宫内膜异位症通常是良性的,这意味着微环境限制了恶性转化。体细胞突变似乎积极参与子宫内膜异位症的发病和纤维形成,而不是偶然发现。它们在良性病变中的检测强调了该疾病的分子复杂性。进一步的研究应该集中在突变与微环境的相互作用上,以开发分子分类和靶向治疗,通过个性化的方法可能彻底改变子宫内膜异位症的治疗。
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引用次数: 0
Mechanistic target of rapamycin inhibitors for fertility preservation in breast cancer: a narrative review 雷帕霉素抑制剂在乳腺癌中保存生育能力的机制靶点:叙述性综述
Pub Date : 2025-09-05 DOI: 10.1016/j.xfnr.2025.100097
Yuji Tanaka M.D., Ph.D., Tsukuru Amano M.D., Ph.D., Ayako Inatomi M.D., Ph.D., Tetsuro Hanada M.D., Ph.D., Akimasa Takahashi M.D., Ph.D., Shunichiro Tsuji M.D., Ph.D.
Breast cancer is the most common malignancy in adolescent and young adult women and poses a high risk of infertility because of gonadotoxic chemotherapy and prolonged endocrine therapy-associated ovarian aging. Although embryo and oocyte cryopreservation are standard approaches, technical limitations (e.g., insufficient oocyte yield) as well as nontechnical barriers, including limited accessibility, cost, and concerns about oncologic outcomes, restrict their use. Ovarian tissue cryopreservation, a backup strategy, also faces the challenge of substantial follicle loss during processing. These gaps underscore the urgent need for pharmacologic ovarian protective agents. Mechanistic target of rapamycin (mTOR) inhibitors, approved for advanced/recurrent breast cancer treatment, have emerged as promising dual-purpose agents that preserve ovarian reserve while enhancing antitumor efficacy. In preclinical models, mTOR inhibition mitigates follicular loss induced by chemotherapy, aging, and ovarian tissue cryopreservation and transplantation. Moreover, mTOR inhibitors may act as endometrial protectants by reducing tamoxifen-induced endometrial hyperplasia. Despite compelling preclinical evidence, clinical application of mTOR inhibitors for fertility preservation remains unexplored. Dedicated trials with coprimary endpoints of ovarian function and oncologic outcomes are warranted. Alternatively, post hoc analyses of existing (neo)adjuvant breast cancer trials could rapidly assess fertility-protective effects. Teratogenic risk appears low, and ovarian-protective doses may be lower than antitumor doses, potentially minimizing toxicity. This narrative review integrates preclinical findings, examines translational challenges, and outlines future directions. Further research on mTOR inhibitors could improve fertility and quality of life for adolescent and young adult survivors.
乳腺癌是青少年和年轻成年女性中最常见的恶性肿瘤,由于促性腺毒性化疗和与卵巢衰老相关的长期内分泌治疗,乳腺癌具有很高的不孕症风险。虽然胚胎和卵母细胞冷冻保存是标准方法,但技术限制(例如,卵母细胞产量不足)以及非技术障碍,包括有限的可及性,成本和对肿瘤结果的担忧,限制了它们的使用。卵巢组织冷冻保存作为一种后备策略,在处理过程中也面临着大量卵泡丢失的挑战。这些空白强调了迫切需要药理学卵巢保护剂。雷帕霉素(mTOR)机制靶点抑制剂已被批准用于晚期/复发性乳腺癌的治疗,作为一种有希望的双重用途药物,在增强抗肿瘤疗效的同时保留卵巢储备。在临床前模型中,mTOR抑制可减轻化疗、衰老、卵巢组织冷冻保存和移植引起的卵泡丢失。此外,mTOR抑制剂可能通过减少他莫昔芬诱导的子宫内膜增生而起到子宫内膜保护作用。尽管有令人信服的临床前证据,mTOR抑制剂在保留生育能力方面的临床应用仍未得到探索。以卵巢功能和肿瘤预后为主要终点的专门试验是必要的。另外,现有的(新)辅助乳腺癌试验的事后分析可以快速评估生育保护作用。致畸风险似乎很低,卵巢保护剂量可能低于抗肿瘤剂量,潜在地减少毒性。这篇叙述性综述整合了临床前研究结果,探讨了转化挑战,并概述了未来的方向。对mTOR抑制剂的进一步研究可以提高青少年和年轻成人幸存者的生育能力和生活质量。
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引用次数: 0
Final oocyte maturation for in vitro fertilization: a comprehensive review with investigators’ recommendations 体外受精的最终卵母细胞成熟:研究人员建议的综合综述
Pub Date : 2025-07-30 DOI: 10.1016/j.xfnr.2025.100096
Evelina Manvelyan M.D. , Agnes Manvelyan M.D. , Kathryn Coyne M.D. , Rebecca Flyckt M.D. , Rachel Weinerman M.D.
The use of gonadotropin-releasing hormone (GnRH) antagonist protocols in assisted reproductive technology provides various options for achieving final follicular maturation. The choice of agent should be tailored to the patient characteristics and the mechanism of action of the triggers. The two primary agents used for this purpose are human chorionic gonadotropin, which acts as a luteinizing hormone analogue, and GnRH agonist, which induces the release of internal gonadotropin stores. Although these agents aim to achieve the same goal, they differ in the mechanism of action and downstream effects. Human chorionic gonadotropin binds to the luteinizing hormone receptors in the ovarian follicles and promotes oocyte maturation and ovulation through continuous luteotropic activity. This prolonged effect can increase the risk of ovarian hyperstimulation syndrome. GnRH agonists trigger ovulation by stimulating an endogenous gonadotropin surge. This process more closely resembles natural ovulation but is transient because of the short half-life. Another option is the dual trigger approach, when human chorionic gonadotropin is combined with GnRH agonist with the aim to optimize oocyte maturation while balancing safety and efficacy. Understanding the underlying mode of action of the triggers is crucial for tailoring individualized treatment protocols, achieving optimal oocyte yield and quality, enhancing clinical outcomes while appropriately mitigating the risks. With this manuscript, we aim to provide an in-depth review of each ovulation trigger agent and their combination and summarize recommendations on the basis of the most common patient characteristics.
在辅助生殖技术中使用促性腺激素释放激素(GnRH)拮抗剂方案为实现最终卵泡成熟提供了多种选择。药物的选择应根据患者的特点和触发因素的作用机制而定。用于此目的的两种主要药物是人绒毛膜促性腺激素,其作为黄体生成素类似物,和GnRH激动剂,其诱导释放内部促性腺激素储存。虽然这些药物的目的是相同的,但它们的作用机制和下游效应不同。人绒毛膜促性腺激素与卵泡中的促黄体激素受体结合,通过持续的促黄体活性促进卵母细胞成熟和排卵。这种长期的影响会增加卵巢过度刺激综合征的风险。GnRH激动剂通过刺激内源性促性腺激素激增来触发排卵。这个过程更接近于自然排卵,但由于半衰期短,它是短暂的。另一种选择是双触发方法,当人绒毛膜促性腺激素与GnRH激动剂联合使用时,目的是优化卵母细胞成熟,同时平衡安全性和有效性。了解触发因素的潜在作用模式对于定制个性化治疗方案,实现最佳卵母细胞产量和质量,提高临床结果,同时适当降低风险至关重要。在这篇文章中,我们的目的是对每种排卵触发剂及其组合进行深入的回顾,并根据最常见的患者特征总结建议。
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引用次数: 0
Fertility considerations in individuals affected by human immunodeficiency virus: a scoping review 受人类免疫缺陷病毒影响的个体的生育考虑:范围审查
Pub Date : 2025-06-17 DOI: 10.1016/j.xfnr.2025.100095
Anisha R. Chada M.D. , Kerri E. Andre M.D. , Noor Al-Shibli M.D. , Heather S. Hipp M.D.
<div><h3>Objective</h3><div>Human immunodeficiency virus (HIV) has transformed from an almost universally terminal diagnosis to that of a chronic manageable condition over the last 4 decades. Patients of reproductive age make up the largest proportion of those with HIV. Our aim in this scoping review was to investigate how HIV sequelae, comorbidities, and antiretroviral treatment affect both male fertility and female fertility.</div></div><div><h3>Evidence Review</h3><div>A scoping review identified relevant articles on HIV, fertility, assisted reproductive technology, and HIV treatment. Included articles had one of the following study designs: prospective; retrospective; controlled; randomized controlled; or observational. Articles were excluded if they were of inappropriate study design or published in a non-English language. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines were used to assess eligibility of studies identified through PubMed, and manuscripts were reviewed independently by 2 reviewers.</div></div><div><h3>Results</h3><div>Fifty-nine manuscripts were included in the final qualitative synthesis, including 9 prospective studies, 14 retrospective studies, 35 observational studies, and 1 clinical trial. Articles on male fertility (n = 10) mainly focused on effects of HIV and/or antiretrovirals on semen quality, finding some level of abnormality in semen parameters compared with controls. Small observational studies (n = 4) found statistically significant effects of antiretroviral therapy on semen parameters. Large observational studies (n = 2) examining outcomes for serodiscordant couples pursuing intrauterine insemination with HIV+ male partner showed pregnancy outcomes comparable to those of controls. In studies examining outcomes of in vitro fertilization for serodiscordant couples with HIV+ male partner (n = 5), pregnancy outcomes were comparable to those of controls. In female patients with HIV (n = 7), HIV infection was associated with ovarian dysfunction and/or oligomenorrhea or prolonged amenorrhea. Markers of severe disease, such as a low CD4 count or viremia, were shown to be correlated with lower antimüllerian hormone levels. Three studies illustrated how the effects of comorbidities such as history of smoking, drug use, or pelvic infections can also compound infertility in these patients. Several cohort studies (n = 13) showed increased time to pregnancy, decreased pregnancy rates with and without in vitro fertilization, and an increased risk of spontaneous abortion. Given that the current backbone of preconception and antepartum management of HIV includes dual therapy with nucleoside reverse transcriptase inhibitors (NRTIs), most of the studies (n = 7) focused on NRTI’s potential toxicities such as mitochondrial depletion in gametes. In vitro and animal studies (n = 3) have shown negative implications on oocyte fertilizability and genomic disturbances in offs
在过去的40年里,人类免疫缺陷病毒(HIV)已经从一种几乎普遍的绝症诊断转变为一种可控制的慢性疾病。在艾滋病毒感染者中,育龄患者所占比例最大。我们的目的是研究HIV后遗症、合并症和抗逆转录病毒治疗如何影响男性和女性的生育能力。证据综述范围综述确定了有关艾滋病毒、生育、辅助生殖技术和艾滋病毒治疗的相关文章。纳入的文章具有以下研究设计之一:前瞻性;回顾;控制;随机对照;或观察。研究设计不当或以非英语语言发表的文章被排除在外。系统评价首选报告项目和荟萃分析扩展范围评价指南用于评估通过PubMed确定的研究的合格性,手稿由2位审稿人独立审查。结果最终定性综合纳入59篇文献,包括9项前瞻性研究、14项回顾性研究、35项观察性研究和1项临床试验。关于男性生育能力的文章(n = 10)主要关注艾滋病毒和/或抗逆转录病毒药物对精液质量的影响,发现精液参数与对照组相比有一定程度的异常。小型观察性研究(n = 4)发现抗逆转录病毒治疗对精液参数的影响具有统计学意义。大型观察性研究(n = 2)检查了血清不一致的夫妇与HIV阳性男性伴侣进行宫内人工授精的结局,结果显示妊娠结局与对照组相当。在检查血清不一致的HIV阳性男性伴侣(n = 5)的体外受精结果的研究中,妊娠结局与对照组相当。在感染HIV的女性患者中(n = 7), HIV感染与卵巢功能障碍和/或月经减少或闭经时间延长有关。严重疾病的标志,如低CD4计数或病毒血症,被证明与较低的抗勒氏杆菌激素水平相关。三项研究表明,吸烟史、药物使用史或盆腔感染等合并症也会加重这些患者的不孕症。几项队列研究(n = 13)显示,妊娠时间延长,有无体外受精的妊娠率降低,自然流产的风险增加。鉴于目前的孕前和产前艾滋病毒管理主要包括核苷类逆转录酶抑制剂(NRTI)的双重治疗,大多数研究(n = 7)集中在NRTI的潜在毒性,如配子中的线粒体耗损。体外和动物研究(n = 3)显示了对后代卵母细胞受精率和基因组紊乱的负面影响。结论HIV感染和治疗均可影响男性和女性的生育能力。人类免疫缺陷病毒阳性的男性精液参数异常的风险更高,更严重的疾病状态加剧了这种风险。人类免疫缺陷病毒阳性的妇女少经或长时间闭经的风险较高,更晚期的疾病可能对卵巢储备产生负面影响。这些妇女可能会经历怀孕率和活产率下降以及自然流产率上升。抗逆转录病毒治疗大大降低了围产期传播的风险;然而,nrti与线粒体消耗有关,对男性和女性配子都有潜在影响。
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引用次数: 0
Fertility care in transgender and gender-diverse individuals: the possibility of oocyte and sperm cryopreservation after medical transition 跨性别和性别多样化个体的生育护理:医学转变后卵母细胞和精子冷冻保存的可能性
Pub Date : 2025-06-04 DOI: 10.1016/j.xfnr.2025.100093
Kyle Le M.D. , Atoosa Ghofranian M.D. , Kate Devine M.D.
Some transgender and gender-diverse individuals desire biological children; however, only a small percentage of these individuals preserve their fertility. There are many barriers preventing such patients from accessing assisted reproductive technologies. Many of them are not informed regarding fertility preservation options before initiation of gender-affirming hormonal therapy (GAHT). Transgender women and transfeminine individuals have worse semen parameters than cisgender men, even without exposure to GAHT. For those who seek GAHT, estradiol and/or antiandrogens may negatively impact semen parameters. Although a hiatus from GAHT before sperm cryopreservation may be considered, this may impose hardship. Transgender men and transmasculine individuals on GAHT have similar oocyte retrieval outcomes compared with transgender men not on GAHT and cisgender women. Multiple reports have indicated positive outcomes even in those who continue their testosterone through the oocyte stimulation cycle. Ideally, transgender and gender-diverse individuals should see a reproductive endocrinologist for a discussion of fertility preservation options and, if desired, should ideally complete fertility preservation before starting GAHT. Still, for several reasons, patients may decline or omit this step before initiating medical transition and then decide later that they wish to pursue fertility preservation or treatment. Thankfully for transgender males, data indicates that successful fertility preservation is possible even after medical transition. For transgender females, estradiol may reduce fertility potential, and outcomes after medical transition can be more limited.
一些跨性别者和性别多样化的个体渴望生儿育女;然而,这些个体中只有一小部分能保持生育能力。有许多障碍阻碍这类患者获得辅助生殖技术。她们中的许多人在开始确认性别的激素治疗之前没有被告知保留生育能力的选择。跨性别女性和跨性别个体的精液参数比顺性男性差,即使没有接触过GAHT。对于那些寻求GAHT的人,雌二醇和/或抗雄激素可能会对精液参数产生负面影响。虽然可以考虑在精子冷冻保存之前暂停使用GAHT,但这可能会带来困难。跨性别男性和跨性别男性与未接受GAHT治疗的跨性别男性和顺性别女性相比,获得卵母细胞的结果相似。多个报告表明,即使在那些通过卵母细胞刺激周期继续使用睾酮的患者中,也有积极的结果。理想情况下,跨性别和性别多样化的个体应该去看生殖内分泌学家,讨论保留生育能力的选择,如果需要的话,应该在开始GAHT之前完成保留生育能力。然而,由于一些原因,患者在开始医疗过渡之前可能会拒绝或省略这一步,然后再决定他们希望继续保留生育能力或治疗。值得庆幸的是,对于跨性别男性来说,数据表明,即使在医学转变之后,成功的生育能力保留是可能的。对于跨性别女性,雌二醇可能会降低生育潜力,并且医学转变后的结果可能更有限。
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引用次数: 0
Blastocyst development in assisted reproductive technologies: a narrative review evaluating its role as a surrogate marker for pregnancy outcomes and live birth success 辅助生殖技术中的囊胚发育:评价其作为妊娠结局和活产成功的代孕标志物作用的叙述性综述
Pub Date : 2025-06-04 DOI: 10.1016/j.xfnr.2025.100094
Dean E. Morbeck Ph.D. , Michael P. Diamond M.D.
There is an urgent global need to improve in vitro fertilization success rates and expand access to services. Specific to the in vitro fertilization laboratory, challenges such as standardization and a shortage of trained embryologists hinder quality and limit service availability. Current standards for product approval rely on demonstrating comparable pregnancy rates, requiring extensive patient involvement and time-consuming trials, which may be further hindered by patient reluctance to participate in clinical trials. Efficient assessment of new protocols and devices for assessing human assisted reproductive technology requires considering intermediate endpoints and markers to complement conventional endpoints. This review explores blastocyst development as a potential surrogate marker for pregnancy. It examines the correlation between blastocyst development and implantation potential, evaluates how culture conditions and other factors affect outcomes, and discusses the evidence supporting an absence of adverse effects of embryo culture on perinatal and offspring health. The conclusion strongly suggests that blastocyst development could serve as a valuable surrogate for establishing equivalency of pregnancy and live births in new assisted reproductive technology protocols. This review underscores the need for a surrogate marker of quality and presents evidence supporting the utility of blastocyst use rate as a sufficient indicator.
全球迫切需要提高体外受精成功率和扩大获得服务的机会。具体到体外受精实验室,标准化和缺乏训练有素的胚胎学家等挑战阻碍了质量并限制了服务的可用性。目前的产品批准标准依赖于证明可比的妊娠率,需要广泛的患者参与和耗时的试验,这可能会因患者不愿参加临床试验而进一步受阻。有效评估评估人类辅助生殖技术的新方案和设备需要考虑中间终点和标记,以补充传统终点。这篇综述探讨了囊胚发育作为妊娠的潜在代孕标志。研究了囊胚发育与着床潜力之间的相关性,评估了培养条件和其他因素如何影响结果,并讨论了支持胚胎培养对围产期和后代健康没有不利影响的证据。该结论强烈提示,在新的辅助生殖技术方案中,囊胚发育可以作为建立妊娠和活产等效性的有价值的替代品。这篇综述强调需要一个质量的替代标记,并提供证据支持囊胚使用率作为一个充分的指标的效用。
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引用次数: 0
Retraction notice to ‘The impact of an endometrial receptivity array on personalizing embryo transfer for patients with infertility: a meta-analysis’ (F S Rev 2022;3:157-73) 撤回“子宫内膜容受性阵列对不孕症患者个性化胚胎移植的影响:一项荟萃分析”(F S Rev 2022;3:157-73)
Pub Date : 2025-06-01 DOI: 10.1016/j.xfnr.2024.100080
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引用次数: 0
Immunocompetent mouse models of endometriosis: a systematic review and meta-analysis 子宫内膜异位症免疫小鼠模型:系统回顾和荟萃分析
Pub Date : 2025-04-24 DOI: 10.1016/j.xfnr.2025.100091
John Coté M.D. , Remington Coté C.P.T. , Isabella Zent B.S. , Kate Woods B.S. , Katherine Kedeshian B.S. , Mya Hendry B.S. , Kaylee Dykstal M.D. , Ryan W. Walters Ph.D.

Objective

To synthesize and compare measurable parameters researchers have used in the different immunocompetent mouse models of endometriosis.

Evidence Review

A systematic literature search of English language studies within PubMed/MEDLINE, Scopus, and Google Scholar from inception until January 2024 was performed. We included studies that reported an immunocompetent mouse model of intra-abdominal endometriosis and recorded at least one quantifiable lesion measurement with associated SDs or standard errors.

Results

The systematic search retrieved 1,421 studies, of which 236 underwent a full text review. A total of 163 studies met inclusion criteria for the meta-analysis. Within the suture (n = 76 studies) and injection (n = 88 studies) models there were multiple outcomes evaluated. The overall effect for lesion weight (33.1 mg, 95% confidence interval [CI], 23.8–45.9), lesion volume (15.6 mm3, 95% CI, 12.2–19.9), lesion area (8.6 mm2, 95% CI, 5.6–13.4), lesion diameter (3.8 mm, 95% CI, 2.8–5.2), and lesion number (3.33, 95% CI, 2.8–3.8). Significant heterogeneity was observed for all outcomes. Meta-regression showed BALB/c strain, days of disease, and receiving estrogen affected lesion weight, injection, days of disease, and autologous donor/recipient affected lesion volume, days of disease affected lesion area, days of disease, and myometrium plus endometrium affected lesion diameter and BALB/c, receiving estrogen, and autologous donor/recipient affected lesion number.

Conclusion

The degree of heterogeneity, risk of bias, and low quality of evidence emphasize the need for a call to action. Model standardization, agreed on by the clinical and translational research community, would improve reproducibility and allow for evidenced-based translational outcomes, especially in the setting of preclinical endometriosis studies.
目的综合比较不同免疫功能小鼠子宫内膜异位症模型的测量参数。对PubMed/MEDLINE、Scopus和谷歌Scholar中从创立到2024年1月的英语语言研究进行了系统的文献检索。我们纳入了报道腹腔内子宫内膜异位症免疫功能小鼠模型的研究,并记录了至少一种可量化的病变测量,伴有相关SDs或标准误差。结果系统检索了1421项研究,其中236项进行了全文综述。共有163项研究符合meta分析的纳入标准。在缝合(n = 76项研究)和注射(n = 88项研究)模型中,评估了多种结果。病变重量(33.1 mg, 95%可信区间[CI], 23.8-45.9)、病变体积(15.6 mm3, 95% CI, 12.2-19.9)、病变面积(8.6 mm2, 95% CI, 5.6-13.4)、病变直径(3.8 mm, 95% CI, 2.8-5.2)和病变数量(3.33,95% CI, 2.8-3.8)的总体效果。所有结果均观察到显著的异质性。meta回归显示BALB/c株、发病天数、接受雌激素影响病变重量、注射、发病天数、自体供体/受体影响病变体积、发病天数、病变面积、发病天数、肌层+子宫内膜影响病变直径和BALB/c、接受雌激素、自体供体/受体影响病变数量。结论异质性程度、偏倚风险和证据质量较低,表明有必要呼吁采取行动。临床和转化研究界一致同意的模型标准化将提高可重复性,并允许基于证据的转化结果,特别是在临床前子宫内膜异位症研究中。
{"title":"Immunocompetent mouse models of endometriosis: a systematic review and meta-analysis","authors":"John Coté M.D. ,&nbsp;Remington Coté C.P.T. ,&nbsp;Isabella Zent B.S. ,&nbsp;Kate Woods B.S. ,&nbsp;Katherine Kedeshian B.S. ,&nbsp;Mya Hendry B.S. ,&nbsp;Kaylee Dykstal M.D. ,&nbsp;Ryan W. Walters Ph.D.","doi":"10.1016/j.xfnr.2025.100091","DOIUrl":"10.1016/j.xfnr.2025.100091","url":null,"abstract":"<div><h3>Objective</h3><div>To synthesize and compare measurable parameters researchers have used in the different immunocompetent mouse models of endometriosis.</div></div><div><h3>Evidence Review</h3><div>A systematic literature search of English language studies within PubMed/MEDLINE, Scopus, and Google Scholar from inception until January 2024 was performed. We included studies that reported an immunocompetent mouse model of intra-abdominal endometriosis and recorded at least one quantifiable lesion measurement with associated SDs or standard errors.</div></div><div><h3>Results</h3><div>The systematic search retrieved 1,421 studies, of which 236 underwent a full text review. A total of 163 studies met inclusion criteria for the meta-analysis. Within the suture (n = 76 studies) and injection (n = 88 studies) models there were multiple outcomes evaluated. The overall effect for lesion weight (33.1 mg, 95% confidence interval [CI], 23.8–45.9), lesion volume (15.6 mm<sup>3</sup>, 95% CI, 12.2–19.9), lesion area (8.6 mm<sup>2</sup>, 95% CI, 5.6–13.4), lesion diameter (3.8 mm, 95% CI, 2.8–5.2), and lesion number (3.33, 95% CI, 2.8–3.8). Significant heterogeneity was observed for all outcomes. Meta-regression showed BALB/c strain, days of disease, and receiving estrogen affected lesion weight, injection, days of disease, and autologous donor/recipient affected lesion volume, days of disease affected lesion area, days of disease, and myometrium plus endometrium affected lesion diameter and BALB/c, receiving estrogen, and autologous donor/recipient affected lesion number.</div></div><div><h3>Conclusion</h3><div>The degree of heterogeneity, risk of bias, and low quality of evidence emphasize the need for a call to action. Model standardization, agreed on by the clinical and translational research community, would improve reproducibility and allow for evidenced-based translational outcomes, especially in the setting of preclinical endometriosis studies.</div></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":"6 2","pages":"Article 100091"},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144138207","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
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 : 2025-03-27 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。
{"title":"In vivo gamete toxicology in the context of in vitro fertilization: a narrative review","authors":"Morgan Orsolini M.S. ,&nbsp;Jason Russack M.S. ,&nbsp;Huey Huynh M.S. ,&nbsp;Douglas Raburn Ph.D. ,&nbsp;John Fox Ph.D. ,&nbsp;Danny Schust M.D.","doi":"10.1016/j.xfnr.2025.100090","DOIUrl":"10.1016/j.xfnr.2025.100090","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":73011,"journal":{"name":"F&S reviews","volume":"6 1","pages":"Article 100090"},"PeriodicalIF":0.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143877101","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
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