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Ovarian Hyperstimulation: Diagnosis, Prevention, and Management. 卵巢过度刺激:诊断、预防和管理。
IF 2.7 3区 医学 Q2 Medicine Pub Date : 2021-11-01 Epub Date: 2021-10-13 DOI: 10.1055/s-0041-1736492
Paolo Emanuele Levi-Setti, Noemi Di Segni, Clara Gargasole, Camilla Ronchetti, Federico Cirillo

Ovarian hyperstimulation syndrome (OHSS) is a severe complication of controlled ovarian stimulation (COS). Pathogenesis of the disease is based on massive transudation of protein-rich fluid from the vascular compartment into the peritoneal, pleural and pericardial spaces, with a variable picture of clinical manifestations depending on its severity. Nowadays OHSS can easily be avoided by several prevention methods, ranging from identification of high-risk patients, choice of a correct protocol stimulation, trigger with gonadotropin-releasing hormone (GnRH) agonists or, finally, the freeze-all strategy. When OHSS occurs, it can usually be managed as outpatient care. Only if severe/critical cases are diagnosed hospitalization is necessary for appropriate rehydration, monitoring of fluid balance and eventual drainage of ascitic fluid. One of the most dangerous complications of OHSS is venous thromboembolism (VTE). Thromboprophylaxis has shown to be cost effective and widely used, while there are controversies regarding the usage of low dose aspirin (LDA) as a preventive measure.

卵巢过度刺激综合征(OHSS)是控制性卵巢刺激(COS)的严重并发症。该病的发病机制是基于富含蛋白质的液体从血管室大量转流到腹膜、胸膜和心包间隙,其临床表现因其严重程度而异。现在,通过几种预防方法可以很容易地避免OHSS,包括识别高危患者,选择正确的方案刺激,使用促性腺激素释放激素(GnRH)激动剂触发,或者最后,冻结所有策略。当OHSS发生时,通常可以作为门诊护理进行管理。只有在诊断出严重/危重病例时,才需要住院进行适当的补液,监测液体平衡并最终排出腹水。OHSS最危险的并发症之一是静脉血栓栓塞(VTE)。血栓预防已被证明具有成本效益和广泛应用,而关于使用低剂量阿司匹林(LDA)作为预防措施存在争议。
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引用次数: 3
Time-Lapse Systems: A Comprehensive Analysis on Effectiveness. 延时系统:有效性的综合分析。
IF 2.7 3区 医学 Q2 Medicine Pub Date : 2021-11-01 Epub Date: 2022-01-10 DOI: 10.1055/s-0041-1742149
Patricia Fadon, Eleanor Gallegos, Salonika Jalota, Lourdes Muriel, Cesar Diaz-Garcia

Time-lapse systems have quickly become a common feature of in vitro fertilization laboratories all over the world. Since being introduced over a decade ago, the alleged benefits of time-lapse technology have continued to grow, from undisturbed culture conditions and round the clock, noninvasive observations to more recent computer-assisted selection of embryos through the development of algorithms. Despite the global uptake of time-lapse technology, its real impact on clinical outcomes is still controversial. This review aims to explore the different features offered by time-lapse technology, discussing incubation, algorithms, artificial intelligence and the regulation of nonessential treatment interventions, while assessing evidence on whether any benefit is offered over conventional technology.

延时系统已迅速成为世界各地体外受精实验室的共同特点。自从十多年前引入延时技术以来,所谓的延时技术的好处不断增加,从不受干扰的培养条件和全天候无创观察到最近通过算法开发的计算机辅助胚胎选择。尽管全球都在采用延时技术,但它对临床结果的真正影响仍然存在争议。本综述旨在探讨延时技术提供的不同功能,讨论孵化、算法、人工智能和非必要治疗干预的监管,同时评估是否比传统技术有任何益处的证据。
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引用次数: 1
Sperm Selection Technology in ART. ART中的精子选择技术。
IF 2.7 3区 医学 Q2 Medicine Pub Date : 2021-11-01 Epub Date: 2021-07-13 DOI: 10.1055/s-0041-1732313
Catherine Martin, Emma Woodland

Intracytoplasmic sperm injection (ICSI) is a commonly used in vitro fertilization technique. Selection of sperm for injection is currently done using subjective assessment of morphology, which may not accurately identify the best-quality sperm. Hyaluronic acid receptors on sperm plasma membranes are a marker of maturity, and sperms which are capable of binding immobilized hyaluronic acid in vitro are of higher quality. This can be used as an advanced sperm selection technique to choose sperm for ICSI, termed physiological ICSI (PICSI). Several studies reported improved fertility treatment outcomes when using PICSI compared with conventional ICSI; however, the majority of studies are underpowered. Recently, a large, multicenter, randomized controlled trial, known as the Hyaluronic Acid Binding Sperm Selection (HABSelect) trial, found a significant reduction in miscarriage rates with PICSI, but no significant effect on live birth rate. There are still many avenues through which PICSI may provide an advantage, subject to confirmation by future research, such as improved long-term health of offspring. Other advanced sperm selection techniques include intracytoplasmic morphologically selected sperm injection, magnetic-activated cell sorting, and Zeta potential sperm selection; however, the most recent Cochrane review concluded that there is currently insufficient evidence to ascertain whether these techniques improve clinical outcomes, such as live birth rates.

胞浆内单精子注射(ICSI)是一种常用的体外受精技术。注射精子的选择目前是通过主观的形态评估来完成的,这可能无法准确地识别出最优质的精子。精子质膜上的透明质酸受体是精子成熟的标志,能够在体外结合固定透明质酸的精子质量较高。这可以作为一种先进的精子选择技术来选择精子进行ICSI,称为生理ICSI (PICSI)。一些研究报告,与传统ICSI相比,使用PICSI可改善生育治疗结果;然而,大多数研究都是缺乏动力的。最近,一项大型、多中心、随机对照试验,即透明质酸结合精子选择(HABSelect)试验,发现PICSI可以显著降低流产率,但对活产率没有显著影响。PICSI仍有许多可能提供优势的途径,有待于未来研究的证实,例如改善后代的长期健康。其他先进的精子选择技术包括胞浆内形态选择精子注射、磁激活细胞分选和Zeta电位精子选择;然而,最近的Cochrane综述得出结论,目前还没有足够的证据来确定这些技术是否能改善临床结果,如活产率。
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引用次数: 5
Thrombophilia, Antithrombotic Therapy, and Recurrent Pregnancy Loss: A Call for Pragmatism in the Face of Unknowns. 血栓病、抗血栓治疗和复发性妊娠丢失:面对未知的实用主义呼吁。
IF 2.7 3区 医学 Q2 Medicine Pub Date : 2021-11-01 Epub Date: 2021-11-08 DOI: 10.1055/s-0041-1735628
Gregory Piazza, Elvira Grandone
A diagnosis of recurrent pregnancy loss (RPL) may represent one of the darkest times for a couple trying to build a family. While aneuploidy and anatomical or functional abnormalities of the reproductive systemmayexplain someRPLs,many patients are left without an explanation for recurrent miscarriages, andmore importantly, without a clear therapeutic strategy for conception and live birth. While many of these couples turn to assisted reproductive therapy (ART), failed cycles, especially after transfer of euploid embryos, often result in further physical, emotional, psychological, and financial hardship. Although epidemiological studies suggest inherited and acquired thrombophilia as a potential risk factor for RPL and failed ART cycles, data have not been consistent, and causality remains unproven.1 Furthermore, implementation of treatment strategies to prevent RPL and failed ART cycles, such as antithrombotic and antiplatelet therapy, has been hindered by lack of high-quality randomized controlled trial (RCT) data.2 The design and execution of adequately powered RCTs have been hampered by several obstacles, including scarcity of funding opportunities and slow enrollment.3 Ultimately, the dilemma facing investigators, clinicians, and patients is whether to wait for definitive RCTs that may be logistically difficult to execute or find new and innovative scientific approaches to illuminate the pathway forward. In the absence of adequate data to drive guideline recommendations, some clinicians may be reluctant to prescribe antithrombotic therapy for patients with RPL who may benefit, while others may be too quick and too broad in advising such treatments, resulting in an unfavorable balance of safety and efficacy. The growth in the number of women with RPL undergoing ART in the United States and Europe has steadily outpaced research focused on the link between miscarriage and thrombophilia and potential therapeutic interventions.4,5 Root causes of this dichotomy include limited advocacy and leadership, scarce research funding, and study enrollment challenges. The social stigma of infertility, lack of public awareness surrounding thrombophilia, and limited clinical recognition of thrombosis as a contributor to RPL undermine advocacy efforts that would increase support for such research. Clinical expertise and scientific investigation focused on thrombophilia and infertility are typically limited to a few centers of excellence in each region or country resulting in a paucity of collaborative research networks necessary to champion RCTs. Funding continues to be a key obstacle to definitive research focused on thrombophilia and infertility, especially since RCTs typically incur the greatest expense. While professional societies such as the American Society for Reproductive Medicine (ASRM) and European Society of Human Reproduction and Embryology (ESHRE) provide a critical Elvira Grandone, MD, PhD Gregory Piazza, MD, MS
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引用次数: 2
Sperm DNA Fragmentation. 精子DNA断裂。
IF 2.7 3区 医学 Q2 Medicine Pub Date : 2021-11-01 Epub Date: 2021-10-18 DOI: 10.1055/s-0041-1736261
Stamatios Karavolos

Sperm DNA fragmentation refers to the accumulation of adducts as well as single- or double-strand DNA breaks and reflects the sperm DNA quality. Current data suggest that there are differences in sperm DNA quality among individuals with high or low fertility, and this observation has led to the idea that testing sperm DNA fragmentation could be a useful test of male fertility. However, sperm DNA fragmentation has become one of the most frequently debated topics in reproductive medicine, as there is no agreement about the optimal way to test for DNA fragmentation, the clinically significant level of sperm DNA fragmentation, as well as the best therapeutic options for infertile men. This article presents current evidence related to sperm DNA fragmentation and its role in managing male infertility.

精子DNA断裂是指加合物的积累以及DNA单链或双链断裂,反映了精子DNA的质量。目前的数据表明,在生育能力高或低的个体中,精子DNA质量存在差异,这一观察结果导致了一种想法,即测试精子DNA片段可能是一种有用的男性生育能力测试。然而,精子DNA断裂已成为生殖医学中最常争论的话题之一,因为对DNA断裂的最佳检测方法、精子DNA断裂的临床显著水平以及对不育男性的最佳治疗选择尚无一致意见。本文介绍了目前有关精子DNA碎片及其在男性不育管理中的作用的证据。
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引用次数: 2
The Use of Androgen Priming in Women with Reduced Ovarian Reserve Undergoing Assisted Reproductive Technology. 雄激素启动在辅助生殖技术卵巢储备减少的妇女中的应用。
IF 2.7 3区 医学 Q2 Medicine Pub Date : 2021-11-01 Epub Date: 2021-09-09 DOI: 10.1055/s-0041-1735646
Alison Richardson, Kanna Jayaprakasan

Androgen priming with either dehydroepiandrosterone (DHEA) or testosterone has been suggested as an adjunct to improve in vitro fertilization (IVF) outcomes in women with diminished ovarian reserve (DOR). Numerous studies have investigated the effects of both DHEA and testosterone on IVF outcome. The results were inconsistent, and the quality of most studies is substandard. Meta-analyses have consistently reported that DHEA does appear to significantly improve IVF outcome in women with predicted or proven poor ovarian response (POR), but these have included some normal responders and/or nonrandomized studies. Our meta-analyses including randomized controlled trials (RCTs) incorporating only women with DOR or POR suggest that DHEA confers no benefit. While meta-analyses of RCTs on the use of testosterone in women with DOR or POR showed an improved IVF outcome, most studies included are of low quality with high risk of bias. When analysis of data from studies of only low-risk bias was performed, such a benefit with testosterone was not observed. Although recruitment may well be a challenge, a large, well-designed RCT is, however, still warranted to investigate whether or not androgen priming with either DHEA or testosterone should be recommended as an adjuvant treatment for women with DOR or POR undergoing IVF.

用脱氢表雄酮(DHEA)或睾酮进行雄激素启动已被认为是改善卵巢储备功能减退(DOR)妇女体外受精(IVF)结果的辅助手段。许多研究调查了脱氢表雄酮和睾酮对体外受精结果的影响。结果是不一致的,大多数研究的质量是不合格的。荟萃分析一致报道,DHEA确实显着改善了预测或证实卵巢反应不良(POR)的妇女的体外受精结果,但这些研究包括一些正常反应和/或非随机研究。我们的荟萃分析包括随机对照试验(rct),仅纳入DOR或POR的女性,表明脱氢表雄酮没有益处。虽然对DOR或POR妇女使用睾酮的随机对照试验的荟萃分析显示体外受精结果有所改善,但大多数纳入的研究质量低,偏倚风险高。当仅对低风险偏倚的研究数据进行分析时,没有观察到睾酮的这种益处。尽管招募可能是一个挑战,但一个大型的、设计良好的随机对照试验仍然有必要调查是否应该推荐用脱氢表雄酮或睾酮作为DOR或POR接受体外受精的女性的辅助治疗。
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引用次数: 2
Approach to the Evaluation and Treatment of Venous Thromboembolism in Pregnancy. 妊娠期静脉血栓栓塞的评价与治疗方法探讨。
IF 2.7 3区 医学 Q2 Medicine Pub Date : 2021-11-01 Epub Date: 2021-09-24 DOI: 10.1055/s-0041-1736188
Benjamin Brenner, Elvira Grandone, Alexander Makatsariya, Jamilya Khizroeva, Victoria Bitsadze, Maria Tretyakova

Thrombosis in pregnancy is a major cause of maternal and fetal morbidity and mortality. Risk stratification of venous thromboembolism (VTE) during pregnancy is complex. The hypercoagulability observed in pregnant women can reduce bleeding during childbirth, but may cause thrombosis especially in the presence of additional prothrombotic risk factors such as antiphospholipid antibodies or genetic thrombophilic defects. The availability of large datasets allows for the identification of additional independent risk factors, including assisted reproductive technologies (ARTs), endometriosis, and recurrent pregnancy loss. Data on the risk of VTE linked to COVID-19 in pregnant women are very limited, but suggest that infected pregnant women have an increased risk of VTE. Current guidelines on the prevention and treatment of VTE in pregnancy are based on available, albeit limited, data and mainly present expert opinion. Low-molecular-weight heparins (LMWHs) are the mainstay of anticoagulation to be employed during pregnancy. Administration of LMWH for VTE treatment in pregnancy should be based on the personalized approach, taking into account a weight-based adjusted scheme. During gestation, due to physiological changes, in women at high risk of VTE, monitoring of anti-Xa activity is performed to ensure adequate LMWH dosing. As for the treatment duration for pregnant women with acute VTE, guidelines suggest that anticoagulation should be continued for at least 6 weeks postpartum for a minimum total duration of therapy of 3 months.

妊娠期血栓形成是孕产妇和胎儿发病和死亡的主要原因。妊娠期间静脉血栓栓塞(VTE)的风险分层是复杂的。在孕妇中观察到的高凝性可以减少分娩时的出血,但可能导致血栓形成,特别是在存在其他血栓形成危险因素(如抗磷脂抗体或遗传性血栓性缺陷)的情况下。大数据集的可用性允许识别额外的独立风险因素,包括辅助生殖技术(ARTs)、子宫内膜异位症和复发性妊娠丢失。关于孕妇与COVID-19相关的静脉血栓栓塞风险的数据非常有限,但表明受感染的孕妇发生静脉血栓栓塞的风险增加。目前关于预防和治疗妊娠静脉血栓栓塞的指南是基于现有的(尽管有限的)数据和主要是目前的专家意见。低分子肝素(LMWHs)是妊娠期间抗凝治疗的主要药物。妊娠期静脉血栓栓塞治疗中低分子肝素的给药应基于个性化的方法,并考虑到基于体重的调整方案。在妊娠期间,由于生理变化,静脉血栓栓塞高风险妇女,监测抗xa活性,以确保足够的低分子肝素剂量。对于急性静脉血栓栓塞孕妇的治疗时间,指南建议抗凝治疗应至少持续产后6周,总治疗时间至少为3个月。
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引用次数: 4
Endometrial Factor in Unexplained Infertility and Recurrent Implantation Failure. 不明原因不孕症和反复着床失败的子宫内膜因素。
IF 2.7 3区 医学 Q2 Medicine Pub Date : 2021-11-01 Epub Date: 2021-08-23 DOI: 10.1055/s-0041-1735199
Xavier Santamaria, Carlos Simón

Unexplained infertility (UI) and recurrent implantation failure (RIF) are diagnoses based on failed pregnancy attempts within current infertility treatment models. Both diagnoses are made when fertility is unexplained based on current diagnostic methods and has no clear cause; UI is diagnosed when testing is inconclusive, and RIF is diagnosed after three failed in vitro fertilization cycles. In both cases, interventions are often introduced without an understanding of the cause of the infertility, frequently leading to frustration for patients and caregivers. Here, we review evidence to support an influence of endometrial factor in patients given these poorly defined diagnoses and possible treatments targeting the endometrium to improve outcomes in these patients.

不明原因不孕症(UI)和复发性着床失败(RIF)是基于当前不孕症治疗模式中失败的妊娠尝试的诊断。这两种诊断都是在根据目前的诊断方法无法解释生育并且没有明确原因的情况下做出的;当检测结果不确定时诊断为UI,而在三次体外受精周期失败后诊断为RIF。在这两种情况下,通常在不了解不孕原因的情况下采取干预措施,这经常导致患者和护理人员感到沮丧。在这里,我们回顾证据来支持子宫内膜因子对这些诊断不明确的患者的影响,以及针对子宫内膜的可能治疗来改善这些患者的预后。
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引用次数: 4
A Baby at All Costs? Exploring the Use and Provision of Unproven Adjuvant Treatments in the Context of IVF. 不惜一切代价要个孩子?探索使用和提供未经证实的辅助治疗在体外受精的背景下。
IF 2.7 3区 医学 Q2 Medicine Pub Date : 2021-11-01 Epub Date: 2021-09-09 DOI: 10.1055/s-0041-1731789
Georgina L Jones, Victoria Lang, Nicky Hudson

The year 2018 marked 40 years since the birth of Louise Brown, the first baby born as a result of pioneering in vitro fertilization (IVF) treatment. Since then, advances have seen a wide range of reproductive technologies emerge into clinical practice, including adjuvant treatments often referred to as IVF "add-ons." However, these "optional extras" have faced growing criticism, especially when they have often come at additional financial cost to the patient and have little evidence supporting their efficacy to improve pregnancy or birth rates. Despite this, according to the latest national patient survey by the Human Fertilisation and Embryology Authority, three quarters of patients who had fertility treatment in the United Kingdom in the past two years had at least one type of treatment add-on highlighting the growing demand for these interventions. This article uses a psychosocial perspective to consider the motivations behind patient and clinician behavior along with the wider societal and economic factors that may be impacting upon the increase in the use of adjuvant treatments in fertility clinics more widely. It suggests the reasons fertility patients use unproven "optional extras" are complex, with interpersonal, psychological, and social factors intertwining to generate an increase in the use of IVF add-ons.

2018年是路易丝·布朗出生40周年,她是第一个通过开创性的体外受精(IVF)治疗而出生的婴儿。从那时起,各种生殖技术进入临床实践,包括辅助治疗,通常被称为体外受精“附加组件”。然而,这些“可选择的额外服务”面临着越来越多的批评,特别是当它们往往给患者带来额外的经济成本,并且几乎没有证据支持它们对提高怀孕率或出生率的有效性时。尽管如此,根据人类受精和胚胎学管理局最新的全国患者调查,在过去两年中,在英国接受生育治疗的患者中,有四分之三至少有一种附加治疗,这突显了对这些干预措施日益增长的需求。本文从社会心理角度考虑患者和临床医生行为背后的动机,以及更广泛的社会和经济因素,这些因素可能会影响生育诊所更广泛地使用辅助治疗。研究表明,不孕患者使用未经证实的“可选择的附加功能”的原因是复杂的,人际、心理和社会因素交织在一起,导致体外受精附加功能的使用增加。
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引用次数: 0
The Current Role of Induced Endometrial Trauma (Endometrial Scratch) in Women Undergoing Infertility Treatment. 诱导子宫内膜损伤(子宫内膜划伤)在不孕妇女治疗中的作用。
IF 2.7 3区 医学 Q2 Medicine Pub Date : 2021-11-01 Epub Date: 2021-11-15 DOI: 10.1055/s-0041-1739162
Mostafa Metwally, Stephen Walters, Robin Chatters

Induced endometrial trauma, otherwise known as endometrial scratch is a simple technique that has been rapidly adopted into clinical practice, mainly for women having IVF treatment, in an attempt to increase pregnancy rates. The introduction of endometrial scratch followed early reports of improved clinical pregnancy rates in women with repetitive implantation failure after having the procedure and follows on from evidence from animal models in the early 20th century suggesting that mechanical trauma to the endometrium can induce decidual changes. Due to the ease and low cost of the procedure, it has been rapidly adopted as an add-on to fertility treatments, in many cases where evidence is still lacking. Despite the initial publication of a large number of studies that demonstrated encouraging improvements in pregnancy rates in women who underwent this procedure, these studies were mainly limited by the small sample sizes and heterogeneity of their study populations, leading to limited validity of the evidence provided by these studies. More recently, three large randomized controlled studies have been published that paint a different picture regarding the value of this procedure. This article explores the evolution of the evidence and the current state of endometrial scratch as an adjuvant therapy for women undergoing IVF treatment.

诱导子宫内膜损伤,也被称为子宫内膜划伤,是一种简单的技术,已迅速应用于临床实践,主要用于接受体外受精治疗的妇女,以提高怀孕率。子宫内膜划伤术的引入是由于早期有报道称,子宫内膜划伤术后反复着床失败的妇女的临床妊娠率有所提高,并且是由于20世纪初动物模型的证据表明,子宫内膜的机械损伤可以引起蜕膜变化。由于该过程的简单和低成本,它已被迅速采用作为生育治疗的附加手段,在许多情况下,证据仍然缺乏。尽管最初发表的大量研究表明,接受这种手术的妇女的怀孕率得到了令人鼓舞的改善,但这些研究主要受到样本量小和研究人群异质性的限制,导致这些研究提供的证据的有效性有限。最近,发表了三个大型随机对照研究,描绘了关于该手术价值的不同图景。本文探讨了证据的演变和子宫内膜划伤作为辅助治疗妇女接受IVF治疗的现状。
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引用次数: 0
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Seminars in reproductive medicine
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