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Screening for Y-chromosome microdeletions in a population of infertile males in the Gaza Strip. 在加沙地带不育男性人群中筛查y染色体微缺失。
Ashraf J Shaqalaih, Masood S Abu Halima, Mohammed J Ashour, Fadel A Sharif

Infertility is an extraordinary public health problem in the Arab world, as it affects about 15% of couples seeking children. The male partner is responsible for infertility in approximately half of these cases. Classic microdeletions of the Y-chromosome involving the azoospermia factor (AZF) regions are known to be associated with spermatogenic impairment, and non-obstructive azoospermia must be differentiated on the basis of endocrine evaluation and testicular biopsy. Partial AZFc deletions remain controversial because there is no clear agreement regarding their role in spermatogenic failure. In the current study, 50 fertile males (controls) and 125 patients with primary idiopathic male infertility were studied in order to describe the frequency of Y-chromosome mirodeletions among male infertility patients in the Gaza Strip-Palestine area. No Y chromosome classical microdeletions could be detected in any of the 125 infertile men, suggesting that ethnic factors, genetic background, and Y chromosome haplogroups are key factors in such deletions. On the other hand, six gr/gr and one b1/b3 AZFc partial deletions were detected in the infertile population. The gr/gr deletion was also noted in relatives of four of the six patients with this deletion, and in one of the fertile controls. In conclusion, our study shows that the incidence of Y-chromosome microdeletions in our population is rare; these data suggest that other genetic, epigenetic, nutritional and/or local factors are responsible for impairments in semen parameters observed in this Gazan population. We further hypothesise that the gr/gr deletion is not associated with male infertility, at least in this sub-group.

不孕不育在阿拉伯世界是一个非常严重的公共卫生问题,因为它影响了大约15%想要孩子的夫妇。在这些病例中,大约有一半是男性伴侣造成的。已知涉及无精子症因子(AZF)区域的典型y染色体微缺失与生精功能障碍有关,必须根据内分泌评估和睾丸活检来区分非阻塞性无精子症。部分AZFc缺失仍然存在争议,因为对于它们在生精失败中的作用没有明确的共识。在本研究中,我们研究了50名有生育能力的男性(对照)和125名原发性特发性男性不育症患者,以描述加沙地带-巴勒斯坦地区男性不育症患者中y染色体微缺失的频率。在125例不育男性中均未检测到Y染色体经典微缺失,提示种族因素、遗传背景和Y染色体单倍群是导致此类缺失的关键因素。另一方面,在不育群体中检测到6个gr/gr和1个b1/b3 AZFc部分缺失。在6名有这种缺失的患者中,有4名患者的亲属和一名有生育能力的对照组中也发现了gr/gr缺失。总之,我们的研究表明,y染色体微缺失的发生率在我们的人群是罕见的;这些数据表明,其他遗传、表观遗传、营养和/或当地因素是造成在加沙人口中观察到的精液参数受损的原因。我们进一步假设,至少在这个亚组中,gr/gr缺失与男性不育无关。
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引用次数: 0
Ovarian hyperstimulation syndrome: current views on pathophysiology, risk factors, prevention, and management. 卵巢过度刺激综合征:病理生理学、危险因素、预防和管理的最新观点。
Michael M Alper, Laura P Smith, Eric Scott Sills

Objective: To summarize current views on the pathophysiology, risk factors, prevention, clinical features, and management of Ovarian Hyperstimulation Syndrome (OHSS).

Design: Literature review

Results: OHSS is a condition characterized by increased capillary permeability, and experimental evidence has identified a provocative link to pathologic vasoactive cytokine actions. Although the ultimate physiologic mechanism of OHSS is not yet known, there are well-known risk factors that must be considered during the administration of medications to treat infertility. Clinical features are consequences of third-spaced intravascular fluid, and OHSS may become life-threatening secondary to thromboembolism or compromised pulmonary or cardiovascular function. Cornerstones of prevention have historically included cycle cancellation, coasting, decreased dosing of human chorionic gonadotropin (hCG) trigger, use of an agonist trigger, and cryopreservation of all embryos. Newer methods of prevention include the administration of a dopamine agonist medication. Management options for OHSS include outpatient transvaginal paracentesis, outpatient transabdominal paracentesis, and inpatient hospitalization with or without paracentesis.

Conclusions: OHSS continues to be a serious complication of assisted reproductive therapy (ART), with no universally agreed upon best method of prevention. Coasting and cryopreservation of all embryos are the most commonly used approaches in the literature, but cycle cancellation is the only method that can completely prevent the development of OHSS. Dopamine agonists are currently being investigated to both prevent and improve the clinical course in OHSS. Recent publications suggest that outpatient paracentesis both prevents the need for inpatient hospitalization and is a cost-effective strategy.

目的:综述卵巢过度刺激综合征(OHSS)的病理生理、危险因素、预防、临床特点及治疗等方面的研究进展。设计:文献综述结果:OHSS是一种以毛细血管通透性增加为特征的疾病,实验证据已经确定了与病理性血管活性细胞因子作用的刺激联系。虽然OHSS的最终生理机制尚不清楚,但在治疗不孕症的药物管理过程中,有一些众所周知的危险因素必须考虑。临床特征是第三间隔血管内液体的后果,OHSS可能继发于血栓栓塞或肺或心血管功能受损而危及生命。从历史上看,预防的基础包括周期取消,顺行,减少人绒毛膜促性腺激素(hCG)触发器的剂量,使用激动剂触发器,以及所有胚胎的冷冻保存。较新的预防方法包括使用多巴胺激动剂药物。OHSS的治疗方案包括门诊经阴道穿刺术、门诊经腹部穿刺术、住院或不住院。结论:OHSS仍然是辅助生殖治疗(ART)的严重并发症,没有普遍同意的最佳预防方法。文献中最常用的方法是对所有胚胎进行冻存和冷冻保存,但周期取消是唯一可以完全防止OHSS发生的方法。目前正在研究多巴胺激动剂,以预防和改善OHSS的临床病程。最近的出版物表明,门诊穿刺术既可以防止住院治疗的需要,也是一种具有成本效益的策略。
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引用次数: 0
Hyperfertility, obesity, and stillbirth: new considerations for clinical practice. 多生育,肥胖和死产:临床实践的新考虑。
Louis G Keith, Tawanda Ngorima, Olha M Tsar

This research focuses on two well known phenomenon that regularly confront obstetricians on a worldwide basis. The first is hyperfertility, whose effects are well known within and outside the obstetrics community. The second is obesity, a problem of growing importance throughout the developed and developing world. Each is discussed in view of recently published evidence. In this work, we show how these two concepts interlock and how they represent a substantial clinical challenge to all physicians providing care to reproductive aged women.

这项研究的重点是两个众所周知的现象,经常面对产科医生在世界范围内的基础上。第一种是生育能力过剩,其影响在产科内外都是众所周知的。第二个是肥胖,这是一个在发达国家和发展中国家日益重要的问题。每一个都是根据最近发表的证据来讨论的。在这项工作中,我们展示了这两个概念是如何相互联系的,以及它们是如何对所有提供育龄妇女护理的医生构成实质性的临床挑战的。
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引用次数: 0
Faircare: A new direction for Health Care and Policy in Ireland. 公平保健:爱尔兰保健和政策的新方向。
James Reilly
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引用次数: 0
Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms resulting in suboptimal oocyte maturation: a discussion of folate status, neural tube defects, schizophrenia, and vasculopathy. 亚甲基四氢叶酸还原酶(MTHFR)基因多态性导致次优卵母细胞成熟:叶酸状态、神经管缺陷、精神分裂症和血管病变的讨论。
Pub Date : 2008-07-10 DOI: 10.1186/1743-1050-5-5
Piet Hein Jongbloet, André Lm Verbeek, Martin den Heijer, Nel Roeleveld

Several conditions apparent at birth, e.g., neural tube defects (NTDs) and cardiac anomalies, are associated with polymorphisms in folate-related genes, such as the 677C --> T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene. Similar associations have been established for several constitutional chronic diseases in adulthood, such as schizophrenia, cardiovascular diseases, dementia, and even neoplasias in different organ systems. This spectrum of developmental anomalies and constitutional diseases may be linked to high-risk conceptions related to preovulatory overripeness ovopathy (PrOO). Some developmental anomalies, such as NTDs, are to a large extent prevented by supplementation of folic acid before conception, but supplementation does not seem to prevent cardiovascular disease or cognitive decline. These diverging results can be elucidated by introduction of the PrOO concept, as MTHFR polymorphisms and inherent low folate levels induce both non-optimal maturation of the oocyte and unsuccessful DNA methylation and demethylation, i.e. epigenetic mutations. The PrOO concept is testable and predicts in a random population the following: (1) female carriers of specific genetic MTHFR variants exhibit more ovulatory disturbances and inherent subfecundity traits, (2) descendents from a carrier mother, when compared with those from a wild-type mother, are more frequently conceived in PrOO high-risk conditions and, thus, (3) disadvantaged in life expectancy. If so, some MTHFR polymorphisms represent a novel, genetically determined, PrOO high-risk conception category comparable to those which are environmentally and behaviorly influenced. These high-risk conditions may cause developmental anomalies and defective epigenetic reprogramming in progeny. The interaction between genetic and environmental factors is a plausible mechanism of multifactorial inheritance.

一些出生时明显的疾病,如神经管缺陷(NTDs)和心脏异常,都与叶酸相关基因的多态性有关,如亚甲基四氢叶酸还原酶(MTHFR)基因的677C -> T多态性。类似的关联也存在于成年期的一些体质性慢性疾病中,如精神分裂症、心血管疾病、痴呆,甚至不同器官系统的肿瘤。这一系列发育异常和体质疾病可能与排卵前过熟性卵巢病(PrOO)相关的高危概念有关。一些发育异常,如NTDs,在很大程度上可以通过孕前补充叶酸来预防,但补充叶酸似乎不能预防心血管疾病或认知能力下降。这些不同的结果可以通过引入PrOO概念来解释,因为MTHFR多态性和固有的低叶酸水平会导致卵母细胞的非最佳成熟和不成功的DNA甲基化和去甲基化,即表观遗传突变。PrOO的概念是可测试的,并在随机人群中预测以下情况:(1)特定遗传MTHFR变异的女性携带者表现出更多的排卵障碍和固有的生殖力低下特征;(2)与野生型母亲的后代相比,携带母亲的后代更容易在PrOO高风险条件下受孕,因此,(3)预期寿命不利。如果是这样的话,一些MTHFR多态性代表了一种新的、由基因决定的、与那些受环境和行为影响的高危受孕类别相当的高风险受孕类别。这些高危条件可能导致后代发育异常和有缺陷的表观遗传重编程。遗传因子与环境因子的相互作用是一种合理的多因子遗传机制。
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引用次数: 20
Estrogen level monitoring in artificial frozen-thawed embryo transfer cycles using step-up regime without pituitary suppression: is it necessary? 在人工冻融胚胎移植周期中使用无垂体抑制的强化方案监测雌激素水平:有必要吗?
Pub Date : 2008-07-04 DOI: 10.1186/1743-1050-5-4
Zhihong Niu, Yun Feng, Yijuan Sun, Aijun Zhang, Huiqin Zhang

Background: To discuss the meaning of serum oestradiol monitoring in frozen embryo transfer cycle using hormone replacement without pretreatment with gonadotropin hormone (GnRH) agonist.

Methods: The data from two hundred twelve women undergoing two hundred seventy-four frozen-thawed embryo transfer (FET) cycles was included in this retrospective cohort study. They were detected of serum oestradiol levels and endometrium thicknesses during hormone supplement FET cycles and compared their pregnancy outcomes according to their oestradiol level on progesterone initiation day.

Results: Patients with different levels of serum oestradiol (percentile 0-25th, 25th-75th and 75th-100th) on progesterone initiation day yielded the endometrium thickness of 9.3 +/- 0.12, 8.9 +/- 0.07 and 9.1 +/- 0.11 mm(P > 0.05) and the pregnancy rate of 32.2%, 38.4% and 36.3% (P > 0.05) respectively.

Conclusion: The serum estradiol level did not predict pregnancy success in hormone replacement FET cycles, suggesting that oestradiol monitoring in this method of endometrial preparation is unnecessary.

背景:探讨无促性腺激素(GnRH)激动剂预处理的激素替代冷冻胚胎移植周期血清雌二醇监测的意义。方法:这项回顾性队列研究纳入了来自212名接受274个冷冻解冻胚胎移植周期的妇女的数据。检测她们在激素补充FET周期内的血清雌二醇水平和子宫内膜厚度,并根据她们在黄体酮起始日的雌二醇水平比较她们的妊娠结局。结果:孕酮起始日血清雌二醇水平不同(0 ~ 25、25 ~ 75、75 ~ 100)的患者子宫内膜厚度分别为9.3 +/- 0.12、8.9 +/- 0.07、9.1 +/- 0.11 mm(P > 0.05),妊娠率分别为32.2%、38.4%、36.3% (P > 0.05)。结论:血清雌二醇水平不能预测激素替代FET周期的妊娠成功,提示在这种子宫内膜制备方法中监测雌二醇是不必要的。
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引用次数: 31
Review 审查
Pub Date : 2008-06-10 DOI: 10.1186/1743-1050-5-3
E. Scott Sills
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引用次数: 1
Paternal effects on early embryogenesis. 父系对早期胚胎发生的影响。
Pub Date : 2008-05-16 DOI: 10.1186/1743-1050-5-2
Laszlo Nanassy, Douglas T Carrell

Historically, less attention has been paid to paternal effects on early embryogenesis than maternal effects. However, it is now apparent that certain male factor infertility phenotypes are associated with increased DNA fragmentation and/or chromosome aneuploidies that may compromise early embryonic development. In addition, there is a growing body of evidence that the fertilizing sperm has more function than just carrying an intact, haploid genome. The paternally inherited centrosome is essential for normal fertilization, and the success of higher order chromatin packaging may impact embryogenesis. Epigenetic modifications of sperm chromatin may contribute to the reprogramming of the genome, and sperm delivered mRNA has also been hythesized to be necessary for embryogenesis. There is less information about the epigenetic factors affecting embryogenesis than genetic factors, but the epigenetics of gamete and early embryogenesis is a rapidly advancing field.

从历史上看,父系对早期胚胎发生的影响比母系的影响更少受到关注。然而,现在很明显,某些男性因素不育表型与DNA片段化和/或染色体非整倍体增加有关,这可能会损害早期胚胎发育。此外,越来越多的证据表明,受精精子的功能不仅仅是携带一个完整的单倍体基因组。父系遗传的中心体对正常受精至关重要,高阶染色质包装的成功可能影响胚胎发生。精子染色质的表观遗传修饰可能有助于基因组的重编程,精子传递的mRNA也被认为是胚胎发生所必需的。表观遗传因素对胚胎发生的影响远远小于遗传因素对胚胎发生的影响,但配子和早期胚胎发生的表观遗传学是一个快速发展的研究领域。
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引用次数: 61
Pregnancy following homologous prepubertal ovarian transplantation in the dog. 犬同种性青春期前卵巢移植后妊娠。
Pub Date : 2008-04-22 DOI: 10.1186/1743-1050-5-1
Jennifer K Pullium, Ross Milner, Gary A Tuma

In several canine models of hereditary human disease the homozygote dogs die prior to puberty, or have substantially reduced fertility. To create a clinically healthy animal that can be bred, but can also transmit the gene of interest, a model of homologous ovarian transplantation in prepubertal dogs was developed. Six dog leukocyte antigen (DLA) identical littermates underwent transplantation of ovarian cortical strips (n = 2) or the entire ovary (n = 4). Immunosuppression was maintained with cyclosporine and MMF in the immediate post-operative period and cyclosporine alone thereafter. All 6 dogs entered puberty and normal semiannual estrus cycles as demonstrated by both physical changes and increasing serum progesterone. Four dogs were bred to a proven stud male, and one became pregnant. Three viable fetuses with observable heart-beats were detected on ultrasound examination. Although the dog eventually aborted the litter, this work represents the first pregnancy achieved following a prepubertal ovarian transplant in the dog.

在几种人类遗传性疾病的犬类模型中,纯合子犬在青春期前死亡,或生育力大幅下降。为了创造一个临床健康的动物,可以繁殖,但也可以传递感兴趣的基因,在青春期前的狗同源卵巢移植模型被开发。6只狗白细胞抗原(DLA)相同的窝鼠分别移植卵巢皮质条(n = 2)或整个卵巢(n = 4)。术后立即使用环孢素和MMF维持免疫抑制,此后单独使用环孢素维持免疫抑制。6只狗均进入青春期,每半年发情一次,身体变化和血清黄体酮水平均有所上升。四只狗被培育成一只雄性种马,其中一只怀孕了。超声检查发现3例可存活的胎儿有明显的心跳。虽然这只狗最终流产了,但这项工作代表了第一次在狗的青春期前卵巢移植后怀孕。
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引用次数: 11
Monozygotic multiple gestation following in vitro fertilization: analysis of seven cases from Japan. 日本体外受精后同卵多胎妊娠7例分析。
Pub Date : 2007-09-22 DOI: 10.1186/1743-1050-4-4
Atsushi Yanaihara, Takeshi Yorimitsu, Hiroshi Motoyama, Hideaki Watanabe, Toshihiro Kawamura

We present a series of monozygous multiple gestations achieved following in vitro fertilization (IVF): one case of monochorionic triplet pregnancy and six cases of dizygotic triplet pregnancy. From September 2000 to December 2006, all patients achieving clinical pregnancy by ART were reviewed (n = 2433). A 37 year-old woman who delivered a healthy singleton after IVF returned two years later for FET, and a single blastocyst was transferred. This also resulted in pregnancy, but TV-USG revealed a single gestational sac with three distinct amniotic sacs, each containing a distinct fetal pole with cardiac activity. This pregnancy was electively terminated at nine weeks' gestation. An additional six cases of dizygotic triplets established after fresh embryo transfer (no ICSI or assisted hatching) are also described. Of these, one resulted in a miscarriage at eight weeks' gestation and five patients have an ongoing pregnancy. This case series suggests the incidence of dizygotic/monochorionic triplets following IVF is approximately 10 times higher than the expected rate in unassisted conceptions, and underscores the importance of a conservative approach to lower the number of embryos at transfer. The role of embryo transfer technique and in vitro culture media in the twinning process requires further study.

我们报告了一系列在体外受精(IVF)后实现的同卵多胎妊娠:一例单绒毛膜三胞胎妊娠和六例异卵三胞胎妊娠。2000年9月至2006年12月,对所有通过ART实现临床妊娠的患者(n = 2433)进行回顾性分析。一名37岁的女性在体外受精后生下了一个健康的单胎,两年后又来做FET,并移植了一个囊胚。这也导致了妊娠,但TV-USG显示了一个单一的妊娠囊和三个不同的羊膜囊,每个羊膜囊包含一个具有心脏活动的不同的胎儿极。妊娠9周时选择性终止妊娠。另外6例异卵三胞胎建立后,新鲜胚胎移植(没有ICSI或辅助孵化)也被描述。其中1例在妊娠8周时流产,5例持续妊娠。本病例系列表明,体外受精后异卵/单绒毛膜三胞胎的发生率约为无辅助受孕的预期发生率的10倍,并强调了采用保守方法减少移植胚胎数量的重要性。胚胎移植技术和体外培养基在双胞胎过程中的作用有待进一步研究。
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引用次数: 26
期刊
Journal of experimental & clinical assisted reproduction
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