p53介导蜕膜化受损致复发性流产的研究进展

复发性流产（RSA）病因复杂,约50%的RSA患者病因不明,其中由于蜕膜化受损所致的胚胎反复丢失成为学者关注的焦点。p53通过参与多种信号通路介导蜕膜化受损从而引发RSA。其中p53/p21信号通路过度激活可干扰细胞周期调控因子的表达,使细胞周期进入停滞状态,蜕膜多倍体化障碍,转而促进细胞凋亡,影响胚胎着床。而在雌二醇（E2）/p53-白血病抑制因子（LIF）-信号转导和转录激活因子3（STAT3）信号通路中,p53在雌激素的协同作用下促进植入期子宫内膜腺体分泌LIF,并激活JAK/STAT信号通路,为胚胎着床创造有利条件。研究表明,参与调控p53信号通路的长链非编码RNA（lncRNA）功能异常及p53通路基因多态性均可影响p53的活性,从而影响蜕膜化及妊娠结局。现就近年来国内外p53蛋白家族及其通路参与蜕膜化的相关研究进行综述。     

维生素D与冻融胚胎移植结局关系的研究进展

冻融胚胎移植（FET）因可提高累积妊娠率,降低多胎率,预防卵巢过度刺激综合征的发生,目前已广泛应用于辅助生殖技术（ART）当中。关于FET妊娠结局的影响因素一直是临床研究关注的热点。近年,随着对维生素D的研究逐渐深入,发现维生素D除参与钙磷代谢、维持骨骼稳态外,还参与卵泡的发育、性激素的产生及胚胎的种植过程。维生素D的缺乏与多种妇科疾病有关,如子宫内膜异位症和多囊卵巢综合征等。目前维生素D在FET领域的研究并不多,且与FET结局之间的关系也尚未明确,本文对近年来维生素D与FET结局关系的研究进展进行综述。     

年龄对卵巢低反应患者辅助生殖技术治疗后活产率的影响及其阈值效应分析

背景卵巢低反应（POR）患者较差的妊娠结局一直是生殖医学领域难题之一,但目前关于年龄对POR患者辅助生殖技术（ART）治疗后活产率的阈值效应的研究少见。目的分析年龄对POR患者ART治疗后活产率的影响及其阈值效应。方法商丘市第一人民医院妇产科和新疆医科大学第一附属医院生殖助孕中心2014年8月至2018年12月共收治接受常规体外授精/卵胞质内单精子注射-胚胎移植（IVF/ICSI）助孕治疗的女性共19 185例,选取其中诊断为POR者共3 337例为研究对象。所有患者采用控制性促排卵方案,同时采用IVF/ICSI进行胚胎移植并给予黄体支持治疗。分析所有患者活产婴儿情况,年龄对POR患者ART治疗后活产婴儿的影响采用单因素和多因素Logistic回归分析,并建立平滑拟合曲线、进行阈值效应分析。结果3 337例POR患者ART治疗后活产婴儿1 134例,未活产婴儿2 203例,活产率为33.98%（1 134/3 337）。多因素Logistic回归分析结果显示,年龄是POR患者ART治疗后活产婴儿的独立影响因素〔OR=0.920,95%CI（0.902,0.939）,P<0.01〕。建立平滑拟合曲线发现,年龄与POR患者ART治疗后活产率呈负相关,但二者之间并非简单的线性关系;阈值效应分析结果显示,POR患者ART治疗后活产率下降的折点为32岁,即年龄≤32岁的POR患者ART治疗后活产率不受年龄影响〔OR=1.000,95%CI（0.998,1.012）,P=0.38〕,但年龄>32岁的POR患者ART治疗后活产率随年龄增长而降低〔OR=0.800,95%CI（0.799,0.823）,P<0.01〕。结论年龄是POR患者ART治疗后活产婴儿的独立影响因素,年龄>32岁的POR患者ART治疗后活产率随年龄增长而降低。     

子宫腺肌病合并不孕的治疗

子宫腺肌病可导致不孕和流产,可增加体外受精-胚胎移植(IVF-ET)的流产率、降低活产率和临床妊娠率,也增加产科和新生儿相关并发症。经阴道超声已成为子宫腺肌病的一线诊断方法,但需提高诊断率。子宫腺肌病合并不孕症的治疗方法包括药物、手术、介入治疗和辅助生殖助孕治疗等。一般情况下可推荐首选IVF,一般推荐GnRH-a的应用和全胚冷冻策略。针对子宫腺肌病的诊断、非IVF治疗方法的效果、GnRH-a预处理以及鲜胚、冻胚移植比较等问题仍需进行更多研究。     

胚胎移植术中胚胎滞留的发生及其对妊娠结局的影响

目的了解胚胎移植术中胚胎滞留的发生率并探讨其对妊娠结局的影响。方法回顾性分析2017年1月至2020年12月于我院生殖中心行IVF-ET助孕的1834个周期的临床资料,根据胚胎移植术中是否发生胚胎滞留分为两组,发生胚胎滞留的为胚胎滞留组(n=65),未发生胚胎滞留的为对照组(n=1769),比较两组患者的一般资料和妊娠结局;同时,根据移植管不同污染因素分为4个亚组,即血液污染组、粘液污染组、渣污染组和未见异常组,比较各亚组的妊娠结局。结果两组患者一般资料比较无显著差异(P>0.05);两组间临床妊娠率、种植率、异位妊娠率、流产率和活产率比较均无显著差异(P>0.05);胚胎滞留组移植管被血液、粘液污染的发生率(分别为24.62%、16.92%)均显著高于对照组(分别为14.09%、7.70%)(P<0.05),而未见异常的发生率显著低于对照组(50.77%vs.71.48%,P<0.05)。在发生胚胎滞留的情况下,移植管血液污染亚组的临床妊娠率显著低于粘液污染亚组和移植管未见异常组(12.5%vs.63.64%、54.55%,P<0.05);在未发生胚胎滞留的情况下,移植管血液污染亚组的临床妊娠率显著低于粘液污染亚组(44.58%vs.55.88%,P<0.05)。结论本研究提示胚胎移植中胚胎滞留未显著影响妊娠结局,但与移植管粘液污染相比,血液污染可能对妊娠结局带来更多的负面影响。     

异常形态精子对植入前胚胎发育和妊娠结局的影响

目的探讨异常形态精子(畸形率≥98%)对植入前胚胎发育及妊娠结局的影响。方法采用回顾性队列研究,分析2017年1~12月在唐都医院妇产科生殖医学中心行ART助孕的2419例患者临床资料,根据异常形态精子分为3组,即IVF对照组(畸形率≤96%,n=2129)、IVF实验组(畸形率≥98%,n=90)和ICSI实验组(畸形率≥98%,n=200)。比较3组间植入前受精失败率(受精率<30%)、正常受精率、可用胚胎率等胚胎发育参数和着床率、临床妊娠率、流产率及活产率等妊娠结局的差异。结果(1)胚胎发育结果:组间比较,IVF实验组受精失败率显著高于IVF对照组(P<0.05),ICSI实验组的受精失败率为0;ICSI实验组正常受精率显著高于IVF对照组和IVF实验组(P<0.05);IVF实验组可用胚胎率显著低于IVF对照组和ICSI实验组(P<0.05)。(2)妊娠结局:单因素分析结果显示,与IVF对照组、ICSI实验组相比,IVF实验组的着床率、临床妊娠率、流产发生率和活产率差异均有统计学意义(P<0.05);IVF对照组和ICSI实验组组间妊娠结局指标比较均无显著性差异(P>0.05)。(3)Logistic多因素分析显示:IVF实验组的受精失败风险显著高于IVF对照组(P=0.002),可用胚胎率、活产率显著低于IVF对照组(P=0.002);ICSI实验组的正常受精率显著高于IVF对照组(P=0.05)。结论对于活力正常、但异常形态精子率≥98%的患者,采用ICSI授精方式,能降低受精失败风险,提高正常受精率和可用胚胎率,同时提高妊娠率和活产率并降低流产发生率。     

Correlation between embryo morphology and development and chromosomal complement

ObjectiveTo analyze the correlation between embryo morphology and the chromosomal status using the array comparative genomic hybridization [array comparative genomic hybridization (a-CGH)] technique for screening 23 chromosome pairs in a single blastomere biopsy from Day 3 embryos.MethodsOne thousand five hundred and fifty seven embryos were included from 203 cycle ICSI patients undergoing preimplantation genetic screening. The 23 chromosome pairs were analyzed by blastomere biopsy from day 3 embryos using a-CGH array method. Embryo development rate, fragmentation rate and chromosome status of the analyzed blastomeres were recorded and correlated with the aCGH results.ResultsThe incidence of chromosomal abnormalities was significantly higher in slow-and fast cleaving embryos at day 3 after insemination. The incidence of fragmentation and the type of fragmentation was associated with an increased incidence of chromosomal abnormalities. The symmetry of the blastomeres also correlated with the aneuploidy rates.ConclusionsEmbryo development rate and morphological parameter such as degree, type of fragmentation and the symmetry of the blastomeres to a large extent reflect the cytogenetic status of the embryo and thus are important in the selection of embryos with the highest implantation potential.     

Ontogeny of adenohypophyseal cells in the pituitary of the American shad (Alosa sapidissima)

The distribution and ontogeny of adenohypophyseal cells have been studied in the pituitary gland of embryos, larvae, and juveniles of the clupeid American shad (Alosa sapidissima) using immunocytochemical techniques. In juvenile specimens, adenohypophysis was composed of rostral pars distalis (RPD), formed by cavities lined by prolactin (PRL), adrenocorticotropic hormone (ACTH), and gonadotropic hormone (GTH) cells; proximal pars distalis (PPD), containing growth hormone (GH), GTH, and putative thyroid stimulating hormone (TSH) cells; and pars intermedia (PI) with somatolactin (SL) and melanophore stimulating hormone (MSH) cells. At 3 days post-fertilization (3 days pre-hatching) the pituitary of embryos consisted of an oval mass of cells, close to the ventral margin of the diencephalon, divided in rostral and caudal regions. At this time PRL and ACTH cells appeared in the rostral region of the adenohypophysis, while SL cells were observed in the caudal region where MSH cells showed reactivity 1 day before hatching. At variance, GH cells showed a weak immunoreactivity in the rostral portion at hatching that increased 2 days latter. GTH cells also showed weak immunoreactivity in the rostral region of the adenohypophysis at hatching time. Two days later GTH cells were located in the rostral and central regions of the adenohypophysis. At hatching, the neurohypophysis was very small and no nerve processes were seen to penetrate the adenohypophysis tissue. After hatching, the pituitary gland elongated and in 7 days old larvae, the RPD showed a small lumen surrounded by a palisade of PRL, ACTH, and GHT cells; the PPD showed GH and GTH cells while the PI contained SL and MSH cells. The adenohypophysis and neural lobe increased in size with development and, in 42 days old larvae, they were similar to those of juvenile specimens.     

基于微流控芯片的动态胚胎培养

目的:在微流控芯片上模拟输卵管收缩和纤毛运动引起的流体机械刺激和生化刺激,发展一种接近生理状态的胚胎动态培养方法,探讨其在体外受精-胚胎培养中的价值。方法:按功能构建微流控芯片,优化流体速度,使小鼠受精卵在芯片微孔中接受持续的灌注培养,同时在芯片上实现胚胎发育的监测。比较用微流控芯片法和常规微滴培养法的胚胎发育情况和囊胚形成率。结果:微流控培养系统流体速度在10μl/h时胚胎发育情况较好,获得的囊胚率最高(47.9%,23/48)。体外受精胚胎在微流控培养组5~8细胞发育率、桑葚胚发育率和囊胚形成率均明显高于微滴培养组(53.1%/46.6%、50.3%/41.5%和45.5%/35.5%),两组之间比较差异均有统计学意义(P均0.05)。而两种培养方法获得的2~4细胞发育率分别为63.4%和60.2%,差异无统计学意义。结论:胚胎培养过程中的物理微环境会影响胚胎质量,这种基于微流控芯片的胚胎动态培养方法可以显著改善胚胎质量,有希望成为辅助生殖技术中胚胎培养的一种新型工具。