卵巢衰老的临床干预新进展

女性生育力的降低显著早于全身机体的衰老,卵巢储备一般在35岁开始下降。目前卵巢衰老的诊断主要依据年龄、基础血FSH、抑制素B和血清抗苗勒氏管激素(AMH)水平及窦卵泡计数。卵巢衰老包括生理性卵巢衰老(NOA)、隐匿性卵巢功能不全(OPOI)和早发性卵巢功能不全(POI)。在IVF周期中补充生长激素、脱氢表雄酮以及辅酶Q10可以部分改善NOA患者的IVF结局。目前针对POI尚无有效的临床治疗手段。卵巢组织玻璃化冷冻联合体外激活的POI临床研究获得了较好的妊娠结局。干细胞移植干预POI患者的临床研究提示其良好的应用前景。逆转卵母细胞衰老的技术中,自体生殖系线粒体能量移植(AUGMENT)在小规模临床试验中能够显著改善卵母细胞的质量和临床妊娠率。本文就卵巢衰老的临床诊断、发病机制和干预方法进行综述。     

基于卵母细胞线粒体探讨早发性卵巢功能不全发生机制

早发性卵巢功能不全是造成女性卵巢功能下降的重要疾病。卵母细胞线粒体是女性生殖系统中的关键细胞器,与卵巢的代谢及其他生理活动息息相关。本文从卵母细胞线粒体功能、卵母细胞线粒体的损伤机理、卵母细胞线粒体与颗粒细胞的联系、卵母细胞线粒体DNA以及卵母细胞线粒体的分裂和融合动态等几个方面探讨了基于卵母细胞线粒体的早发性卵巢功能不全发生机制。同时总结了胞浆移植、异体体细胞线粒体移植以及自体体细胞线粒体移植等治疗早发性卵巢功能不全的方法。     

子宫内膜异位症对卵母细胞和胚胎发育的影响机制研究进展

子宫内膜异位症(EMs)是育龄期女性的常见疾病，与不孕症密切相关。EMs影响卵母细胞质量及胚胎发育，从而引起胚胎种植率下降。然而EMs影响卵母细胞和胚胎的机制还未完全阐明。本文对EMs如何潜在地损害卵母细胞和胚胎的发育潜力的机制进行综述，了解其影响机制有助于理解疾病的复杂性质，以期寻找更合理的方法进行子宫内膜异位症相关性不孕症的诊断、治疗和管理。     

线粒体融合蛋白参与调节女性生殖功能的研究进展

线粒体融合蛋白(mitofusin,Mfn)是一类位于线粒体外膜的三磷酸鸟苷酶,通过促进线粒体的融合进而直接影响线粒体功能,调节线粒体介导的细胞能量产生、自噬及凋亡等。在女性生殖系统中,Mfn在调节卵泡发育、促进窦前卵泡向窦卵泡转化、促进卵母细胞成熟以及维护妊娠期子宫内环境稳态等方面具有重要作用;此外,Mfn还参与多囊卵巢综合征等多种生殖系统相关疾病的病理发展过程,影响辅助生殖技术助孕妊娠结局。深入研究Mfn参与调控女性生殖的过程,可为进一步探索女性生殖发生相关的生物学分子机制,以及为促进女性生殖健康提供新的思路。本文就Mfn对女性生殖功能调控的研究进展进行综述。     

卵母细胞中线粒体相关内质网膜结构与功能的研究进展

在卵母细胞发育成熟过程中,各细胞器之间有效、稳定的交流是保证其功能与质量的基础。内质网作为细胞钙储池,通过耦联结构与线粒体外膜相连,传递Ca²⁺信号,我们称该结构为线粒体相关内质网膜(Mitochondria associated membrane,MAM)。MAM在调控内质网应激、线粒体功能、细胞凋亡等生理活动以及神经退行性病变、心肌衰老等病理变化中多见报道。近年来的研究发现MAM在卵母细胞质量下降机制中也扮演重要角色。本文综述MAM的组成及相关蛋白组分,重点阐述其在卵母细胞成熟与发育中扮演的角色以及相关的研究进展。     

原始卵泡的形成与发育

在胚胎发育时期,原始生殖细胞形成并迁移至生殖腺,形成种系囊。卵原细胞进入减数分裂成为卵母细胞。随后种系囊分裂,单个卵母细胞与前颗粒细胞组装成原始卵泡。前泡膜细胞被募集到原始卵泡周围,原始卵泡发育并向初级卵泡转化。原始卵泡的形成和发育是卵巢生物学的重要过程,阐释其分子和细胞机制为调节卵巢功能和治疗卵巢疾病提供方向。     

卵丘细胞在卵母细胞发育过程中的作用

卵母细胞能否正常发育成熟是影响女性生育能力的重要因素,目前人们普遍认为,人类卵母细胞和卵丘细胞之间的相互交流,对于卵母细胞发育是不可或缺的。在卵泡窦腔形成过程中,颗粒细胞分化为壁颗粒细胞和卵丘细胞,卵丘细胞与其他卵泡细胞不同,具有本身独特的功能、促进排卵前卵母细胞的生长和成熟及支持排卵后卵母细胞功能的作用。本文主要对卵丘细胞的功能及在卵母细胞发育过程中的作用进行论述。     

玻璃化冷冻人卵母细胞的临床应用：附一例成功分娩

人卵母细胞冷冻保存是女性生育力直接保存的一种方法。但由于卵母细胞自身生物学特性的影响,卵母细胞冷冻的妊娠率始终不高。本院采用玻璃化技术冷冻人卵母细胞2例,1例获得临床妊娠,目前已分娩。     

医学抗衰老分子靶向治疗进展

衰老不仅是人类个体健康面临的重要问题,同时也牵动着整个社会的关注。当前,衰老造成的社会经济负担急剧增长,因此衰老及衰老相关疾病的研究也正成为一个新兴的热点领域。近年来,医学抗衰老的内分泌治疗由于其可能增加患肿瘤风险等潜在的多种副作用而受到一定限制,医学抗衰老的研究也已从内分泌信号通路扩展至对衰老相关基因网络及分子靶点的调控。既往的研究证实,GHRH-GH-IGF-1/insulin,TOR-S6K1,NAD~+-Sirtuin,P53,Klotho和APOE等基因靶点和信号通路与肿瘤、心血管疾病、糖尿病、骨质疏松、神经退行性变等衰老相关疾病之间存在紧密联系,是目前抗衰老的关键靶点。深入研究医学抗衰老相关的信号通路及分子靶点,有助于我们更好地了解衰老发生及调控的机制,研发安全有效的抗衰老药物。     

卵母细胞代谢及其调节

卵母细胞发育与成熟过程依赖大量ATP,因此物质代谢旺盛。卵母细胞以葡萄糖和/或其中间产物丙酮酸为底物,在线粒体内氧化磷酸化,产生大量ATP,是卵母细胞最主要的供能形式。但是,卵母细胞糖代谢模式有种属特异性差异。同时,卵母细胞也存在脂肪酸和氨基酸的代谢。除提供能量外,这些代谢产物在细胞信号传导、渗透压调节等方面也有重要作用。卵母细胞代谢的精确调控受多方面因素的影响如卵母细胞胞内、胞间、胞外的调控等。研究卵母细胞代谢及其机制,对探寻改善卵母细胞质量、提高卵母细胞体外成熟效能具有重要的意义。     

Influence of male sexual rest and oocyte aging on parthenogenesis frequency in mice: cytogenetic analysis after in vitro fertilization.

This study was conducted to evaluate the influence of male sexual rest and oocyte aging on fertilization rate and parthenogenesis frequency after in vitro fertilization of mouse oocytes. We used a comparison between cleavage rates and fertilization rates according to chromosomal analysis of oocytes to estimate the parthenogenesis frequency. Fertilization rate was not impaired by male sexual rest. Parthenogenesis frequency was increased by male sexual rest. This effect was enhanced by a concomitant moderate oocyte aging. It is concluded that cleavage rate could not be considered as a reliable test of fertilization after attempted in vitro fertilization in such conditions.     

低剂量17 β雌二醇在赠卵助孕术中的应用

目的：研究恒定、低剂量微粒化17 β雌二醇(诺坤复)在赠卵助孕术中的应用。方法：1999年1月至2000年7月,应用诺坤复1～2 mg/d和黄体酮为43例接受赠卵的患者准备子宫内膜共51个周期,由40例同期行体外受精和胚胎移植(IVF-ET)或配子输卵管内移植术(GIFT)的不孕患者和5名正常妇女提供卵母细胞。结果：供卵和接受赠卵者共移植90个周期,妊娠34例,妊娠率为38%。接受赠卵的51个周期中,临床妊娠20例,供卵者移植39例中,临床妊娠14例,妊娠率分别为39%和36%,两组间无显著差别,妊娠与未妊娠患者之间平均年龄、不孕原因和移植的胚胎数等均无显著差别。结论：在等待赠卵期间,用低剂量(1～2 mg/d)诺坤复可有效地刺激子宫内膜生长,为胚胎移植作准备。     

低剂量17β雌二醇在赠卵助孕术中的应用

目的 :研究恒定、低剂量微粒化 1 7β雌二醇 (诺坤复 )在赠卵助孕术中的应用。方法 :1 999年 1月至 2 0 0 0年 7月 ,应用诺坤复 1～ 2 mg/ d和黄体酮为 43例接受赠卵的患者准备子宫内膜共 5 1个周期 ,由 40例同期行体外受精和胚胎移植 (IVF-ET)或配子输卵管内移植术 (GIFT)的不孕患者和 5名正常妇女提供卵母细胞。结果 :供卵和接受赠卵者共移植 90个周期 ,妊娠 34例 ,妊娠率为 38%。接受赠卵的 5 1个周期中 ,临床妊娠 2 0例 ,供卵者移植 39例中 ,临床妊娠 1 4例 ,妊娠率分别为 39%和 36 % ,两组间无显著差别 ,妊娠与未妊娠患者之间平均年龄、不孕原因和移植的胚胎数等均无显著差别。结论 :在等待赠卵期间 ,用低剂量 (1～ 2 mg/ d)诺坤复可有效地刺激子宫内膜生长 ,为胚胎移植作准备。     

卵子玻璃化冷冻在睾丸取精失败周期中的临床应用(附8例报告)

目的:探讨卵子玻璃化冷冻在睾丸取精失败周期中的临床应用价值。方法:回顾分析体外受精周期取卵日因男方无精子症行睾丸取精失败且无供精接受卵子冷冻的8例不孕症妇女。所有卵子经玻璃化冷冻保存2个月后解冻,存活的成熟卵子采用与其丈夫血型一致的精子库冷冻精子行卵细胞胞质内单精子注射(ICSI)受精,记录卵子的存活、受精、卵裂、优质胚胎、临床妊娠及分娩情况。结果:冷冻-解冻60枚卵子中存活47枚,存活率为78.3%(47/60);其中41枚成熟卵子行ICSI受精,正常受精率为80.5%(33/41),卵裂率为81.8%(27/33),优质胚胎率为59.3%(16/27);15枚胚胎移植给8例患者,移植周期率为100%(8/8),平均移植胚胎数为1.9±0.8。B超显示有5个孕囊形成,胚胎种植率为33.3%(5/15);5例患者获得了临床妊娠,临床妊娠率为62.5%(5/8),均为宫内单活胎。4例已顺利分娩3男婴1女婴,体重为(3 787.5±513.7)g,染色体及发育均正常。结论:卵子玻璃化冷冻是睾丸取精失败患者的有效保障,与精子库冷冻供精受精可以获得理想临床结局。     

35岁以下患者长方案促排卵获卵数对体外受精-胚胎移植结局的影响

目的探讨体外受精-胚胎移植（IVF-ET）周期最佳获卵数及其对妊娠结局的影响。方法回顾性分析我院2009年9月至2010年8月35岁以下行长方案IVF-ET治疗的544个获卵周期的资料。比较不同获卵数的受精率、卵裂率、优胚率、临床妊娠率及并发症等指标的差异。结果不同获卵数各组间促性腺激素（Gn）刺激天数、Gn用量、卵裂率、优胚率无明显差别（P〉0．05）,获卵数〉25个组受精率低于其他各组（P〈0．05）。随获卵数的增加,冷冻胚胎数、注射人绒毛膜促性腺激素（hCG）日血雌二醇（E2）值及卵巢过度刺激综合征（OHSS）发生率增加,差异有统计学意义（P〈0．05）。临床妊娠率随获卵数增加逐渐增加,当获卵数〉15个,临床妊娠率较前下降,累积妊娠率随获卵数增加而增加,当获卵数〉25个,临床妊娠率和累积妊娠率明显下降。结论获得适量的卵有利于获得较满意的妊娠结局。     

Effect of nitrous oxide on propofol requirement during target-controlled infusion for oocyte retrieval

BACKGROUND: Oocyte (egg) retrieval for in-vitro fertilization is a relatively short procedure, usually performed as an outpatient. Propofol is a suitable anesthetic agent. Target-controlled infusion is a recently developed system that aids rapid recovery from propofol anesthesia. This study sought to determine the target concentration of propofol required to prevent movement in 50% (Cp50) and 95% (Cp95) of women during oocyte retrieval, and investigated whether supplemental nitrous oxide (N2O) modified the Cp50 and Cp95. METHODS: Forty-seven women scheduled for oocyte retrieval were randomly selected to receive either O2-air mixture (control group; n = 23) or 50% O2-N2O mixture (Nitrous oxide group; n = 24). Propofol was infused using a target-controlled infusion system with the concentration determined by up-down sequential allocation using 0.5 microg/mL step size. Transvaginal oocyte retrieval was performed after reaching target blood concentration. Patient responses to oocyte retrieval were noted as either no movement or movement. RESULTS: Using target-controlled infusion the Cp50 was 4.1 microg/mL in the control group and 3.3 microg/mL in the nitrous oxide group. Calculated Cp95 values were 4.0 microg/mL and 5.1 microg/mL with and without 50% nitrous oxide respectively. CONCLUSIONS: The Cp50 value for target-controlled infusion propofol during oocyte retrieval was significantly reduced by a factor of 1.24 (95% CI 1.07-1.44) with the use of 50% nitrous oxide.     

Anesthetic impact of body mass index in patients undergoing assisted reproductive technologies

STUDY OBJECTIVE: To determine the prevalence and anesthetic impact of obesity in patients undergoing assisted reproductive technologies. DESIGN: Retrospective analysis of a complete calendar year of oocyte retrieval procedures. SETTING: Center for reproductive medicine of a tertiary care university teaching hospital. PATIENTS: 1,289 ASA physical status I, II, and III women undergoing oocyte retrieval procedures. MEASUREMENTS: Patient demographics, body mass index (BMI), comorbid conditions, frequency and characterization of intraoperative and postoperative events, route of oocyte retrieval, and anesthetic technique were assessed. MAIN RESULTS: Of the 1,289 women, 33% were overweight or obese. The prevalence of gastroesophageal reflux disease, depression/anxiety, hypothyroidism, diabetes, and hypertension was associated with increasing BMI (P < 0.02). Transvaginal oocyte retrieval and the use of total intravenous anesthesia were less common with increasing BMI (P < 0.01; P < 0.003). Oxygen desaturation occurred more frequently intraoperatively and postoperatively in patients with high BMI (P < 0.0001), as did the reports of postoperative discomfort and the need for additional analgesia (P < 0.001). No patients managed with spinal anesthesia experienced intraoperative desaturation or required conversion to general anesthesia with endotracheal intubation. CONCLUSIONS: Patients with high BMI have a greater prevalence of comorbid conditions, require alterations in anesthetic and oocyte retrieval management, and more often experience intraoperative and postoperative events.     

Fertility Preservation for Young Women with Rectal Cancer—A Combined Approach from One Referral Center

Background  Up to 6% of women with colorectal cancer are diagnosed in the reproductive age and are at risk for premature ovarian failure and infertility due to pelvic irradiation and chemotherapy. Study Design  Between 1997 and 2007, six women with rectal carcinoma were referred to the McGill Reproductive Center (Montreal, Canada) for fertility preservation. Following resection of their primary tumor, they were scheduled to undergo pelvic irradiation. Results  Five patients underwent laparoscopic ovarian lateral transposition before radiotherapy in order to relocate their ovaries outside the radiation field. A concomitant ovarian wedge resection was performed for ovarian cryopreservation. In two of these women, before dissecting the ovarian cortical tissue for cryopreservation, all visible follicles were aspirated. The sixth patient who had had low anterior resection underwent hormonal ovarian stimulation followed by oocyte retrieval and embryo vitrification. Conclusions  Fertility preservation in women with rectal cancer is feasible. This includes laparoscopic ovarian transposition and cryopreservation of ovarian tissue, embryo, or oocyte.     

The aging man and woman: are the differences important?

This article celebrates the continuing differences between men and women that are present in our twilight years. Although men die earlier than women, they spend fewer years with major disability. There is increasing interest in the use of testosterone to improve the quality of life in both older men and women. Sarcopenia, osteopenia, hip fractures, and frailty are all more common in women than in men. Sexuality remains important to both men and women throughout life. Finally, it is known that cytokines play a major role in the pathophysiology of aging, a process now recognized as the cytokine-related aging process.