Maternal age

产妇年龄
  • 文章类型: English Abstract
    年龄在35岁及以上的不孕症妇女的治疗在每三分之一的病例中应用辅助生殖技术(ART)。该研究的目的是分析孕产妇健康对35岁及以上妇女在应用ART后分娩的儿童健康的影响。分析,直接观察,社会学(提问),并采用统计学方法。研究35-45岁女性应用ART方法后出生的儿童的健康状况,选择648名学龄前儿童(4-6岁)的代表性主要群体。第二对照组包括649名学龄前儿童(4-6岁),尽可能与主要群体的孩子相同,根据以下特征进行选择:母亲在孩子出生时的年龄(35-45岁),年龄(从4到6岁),都是在同一个医疗机构观察到的,从单身出生,足月(37周或以上)怀孕。主要组和对照组仅在存在或不存在ART方法时彼此不同。早产的孩子,从卵子供体计划和多胎妊娠被排除在研究之外.根据体检对儿童的健康状况进行了研究,医疗记录,儿童发展史,和母亲关于儿童健康的问卷调查数据。怀孕和分娩的过程,根据母亲的问卷调查和门诊医疗记录中的数据副本,研究了母亲的发病率和生活方式特征。确定儿童健康与母亲健康之间存在直接相关性(r=0.571;p<0.01,t=3)。在那,结果表明,由于38-45岁母亲的亚组(3353.7‰和2341.8‰对照组)的显着差异,ART后儿童和自然妊娠儿童的一般发病率水平存在差异。
    The treatment of women aged 35 years and older with infertility applies assisted reproductive technologies (ART) in every third case. The purpose of the study is to analyze impact of maternal health on health of children who were delivered by women aged 35 years and older after application of ART. The analytical, direct observation, sociological (questioning), and statistical methods were applied. To study health status of children born after application of ART methods in women aged 35-45 years, representative main group of 648 preschool children (4-6 years old) was selected. The second control group included 649 preschool children (4-6 years old), who were as identical as possible to children from the main group, selected according to following characteristics: mother\'s age at birth of child (35-45 years), age (from 4 to 6 years), all were observed in same medical organization, birth from a singleton, full-term (37 weeks or more) pregnancy. The main and control groups differed from each other only in presence or absence of ART methods. The children born preterm, from egg donor programs and multiple pregnancies were excluded from study. The children health was studied according to medical examinations, medical records, child development history, and mothers questionnaire data on children health. The course of pregnancy and childbirth, morbidity and lifestyle characteristics of mothers were studied according to their questionnaires and copies of data from their outpatient medical records. It was established that there is direct correlation between health of child and health of mother (r = 0.571; p < 0.01, t = 3). At that, it was revealed that differences in level of general morbidity of children after ART and children from spontaneous pregnancy are achieved within account of significant differences in subgroup of children of mothers aged 38-45 years (3353.7‰ and 2341.8‰ control group).
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  • 文章类型: Journal Article
    在低风险产科医院根据Robson分类评估产后出血(PPH)的危险因素。
    我们通过分析在低风险妇产医院就诊的孕妇的医疗记录,进行了回顾性队列研究,从2019年11月到2021年11月。分析的变量是:产妇年龄,交货类型,出生体重,奇偶校验,罗布森分类,和PPH的原因。我们比较了自发性(第1组和第3组)和引产(2a和4a)孕妇之间PPH的发生率。进行卡方和学生t检验。使用二元逻辑回归比较变量。
    在研究期间有11,935例分娩。根据罗布森的分类,48.2%被分类为1和3(I组:5,750/11,935),26.1%被分类为2a和4a(II组:3,124/11,935)。II组的PPH患病率高于I组(3.5vs.2.7%,p=0.028)。引产使PPH发生率增加18.8%(RR:1.188,95%CI:1.02~1.36,p=0.030)。包括镊子分娩的模型[x2(3)=10.6,OR:7.26,95CI:3.32-15.84,R2Nagelkerke:0.011,p<0.001]和出生体重[x2(4)=59.0,OR:1.001,95CI:1.001-1.001,R2Nagelkerke:0.033,p<0.001]是预测Robson1,3,2a患者PPH的最佳4a。出生体重是PPH的不良预测指标(ROC曲线下面积:0.612,p<0.001,95CI:0.572-0.653)。
    Robson分类2a和4a显示产后出血率最高。在Robson分类1、3、2a中,包含产钳分娩和出生体重的模型是产后出血的最佳预测指标。4a。
    UNASSIGNED: To evaluate the risk factors for postpartum hemorrhage (PPH) according to the Robson Classification in a low-risk maternity hospital.
    UNASSIGNED: We conducted retrospective cohort study by analyzing the medical records of pregnant women attended in a low-risk maternity hospital, during from November 2019 to November 2021. Variables analyzed were: maternal age, type of delivery, birth weight, parity, Robson Classification, and causes of PPH. We compared the occurrence of PPH between pregnant women with spontaneous (Groups 1 and 3) and with induction of labor (2a and 4a). Chi-square and Student t-tests were performed. Variables were compared using binary logistic regression.
    UNASSIGNED: There were 11,935 deliveries during the study period. According to Robson\'s Classification, 48.2% were classified as 1 and 3 (Group I: 5,750/11,935) and 26.1% as 2a and 4a (Group II: 3,124/11,935). Group II had higher prevalence of PPH than Group I (3.5 vs. 2.7%, p=0.028). Labor induction increased the occurrence of PPH by 18.8% (RR: 1.188, 95% CI: 1.02-1.36, p=0.030). Model including forceps delivery [x2(3)=10.6, OR: 7.26, 95%CI: 3.32-15.84, R2 Nagelkerke: 0.011, p<0.001] and birth weight [x2(4)=59.0, OR: 1.001, 95%CI:1.001-1.001, R2 Nagelkerke: 0.033, p<0.001] was the best for predicting PPH in patients classified as Robson 1, 3, 2a, and 4a. Birth weight was poor predictor of PPH (area under ROC curve: 0.612, p<0.001, 95%CI: 0.572-0.653).
    UNASSIGNED: Robson Classification 2a and 4a showed the highest rates of postpartum hemorrhage. The model including forceps delivery and birth weight was the best predictor for postpartum hemorrhage in Robson Classification 1, 3, 2a, and 4a.
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  • 文章类型: Journal Article
    随着我国三孩政策的逐步放开和辅助生殖技术的发展,高危孕妇的数量正在逐渐增加。在这项研究中,分析了4211例接受染色体微阵列分析(CMA)并具有高危产前指征的胎儿。结果显示,CMA的产前总检出率为11.4%(480/4211),染色体异常数检出率为5.82%(245/4211),拷贝数变异检出率为5.58%(235/4211)。此外,临床显著拷贝数变异的检出率分别为3.78%(159/4211)和不确定显著性变异的1.8%(76/4211).高龄孕妇(AMA)胎儿染色体异常检出率为6.42%(30/467),6.01%(50/832)为高危孕产妇血清筛查(MSS)结果,39.09%(224/573)的非侵入性产前检测(NIPT)结果异常,9.21%(127/1379)的超声检查结果异常,其他适应症为5.1%(49/960)。4211名患者获得了随访结果,其中3677名(3677/4211,87.32%)婴儿出生后正常,462名(462/4211,10.97%)终止妊娠,51例(51/4211,1.21%)婴儿出生后异常,21名(21/4211,0.50%)拒绝随访。这项研究的结果表明,不同适应症的染色体微阵列分析的诊断率存在显着差异,为临床医生评估CMA技术在产前诊断中的适用性提供有价值的指导。
    With the gradual liberalization of the three-child policy and the development of assisted reproductive technology in China, the number of women with high-risk pregnancies is gradually increasing. In this study, 4211 fetuses who underwent chromosomal microarray analysis (CMA) with high-risk prenatal indications were analysed. The results showed that the overall prenatal detection rate of CMA was 11.4% (480/4211), with detection rates of 5.82% (245/4211) for abnormal chromosome numbers and 5.58% (235/4211) for copy number variants. Additionally, the detection rates of clinically significant copy number variants were 3.78% (159/4211) and 1.8% (76/4211) for variants of uncertain significance. The detection rates of fetal chromosomal abnormalities were 6.42% (30/467) for pregnant women with advanced maternal age (AMA), 6.01% (50/832) for high-risk maternal serum screening (MSS) results, 39.09% (224/573) with abnormal non-invasive prenatal testing (NIPT) results, 9.21% (127/1379) with abnormal ultrasound results, and 5.1% (49/960) for other indications. Follow-up results were available for 4211 patients, including 3677 (3677/4211, 87.32%) whose infants were normal after birth, 462 (462/4211, 10.97%) who terminated their pregnancy, 51 (51/4211, 1.21%) whose infants were abnormal after birth, and 21 (21/4211, 0.50%) who refused follow-up. The results of this study demonstrate significant variation in the diagnostic rate of chromosomal microarray analysis across different indications, providing valuable guidance for clinicians to assess the applicability of CMA technology in prenatal diagnosis.
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    文章类型: Journal Article
    对具有代表性的“GGP-当代捷克家庭调查”(2020-2022)对40-69岁女性人口的数据进行的分析显示,更年期的发病年龄与第一个孩子出生时的低年龄有关。在20岁生日之前生第一个孩子的女人,1989年以前几代妇女中常见的一种生殖行为模式,其更年期比初产妇更早。相反,首次出生时年龄较高(35岁或以上)对绝经延迟的影响尚未得到证实。然而,这个问题需要进一步调查,因为分析的样本表明了某些趋势。需要更大的样本量才能做出结论性发现。
    Analysis of data from the representative \"GGP - Contemporary Czech Family Survey\" (2020-2022) on the population of women aged 40-69 years showed that the age of onset of menopause is associated with a low age at the birth of the first child. Women who had their first child before their 20th birthday, a pattern of reproductive behaviour common among generations of women before 1989, have an earlier onset of menopause than older first-time mothers. Conversely, the effect of higher age at first birth (35 years or more) on the delay of menopause has not been proved. However, this issue requires further investigation, as the sample analysed suggests certain tendencies. A larger sample size would be needed to make a conclusive finding.
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  • 文章类型: Journal Article
    鉴于日本独特的社会背景,了解当前产后出血(PPH)的危险因素对有效管理病情至关重要,特别是在特定群体中。因此,本研究旨在确定日本计划剖宫产术(CS)中PPH的当前危险因素.这项多中心回顾性队列研究是在福岛的两个三级母胎医学单位进行的,日本包括1,069名在2013年1月1日至2022年12月31日期间接受计划CS的女性。PPH(>1000g和>1500g)的危险因素使用多变量逻辑回归分析进行评估。考虑到诸如产妇年龄等变量,奇偶校验,辅助生殖技术(ART)怀孕,孕前体重指数(BMI),子宫肌瘤,前置胎盘,分娩时的胎龄,出生体重类别,和妊娠高血压疾病(HDP)。进行多元线性回归分析以预测计划CS期间的估计失血量。ART怀孕,孕前BMI为25.0-29.9kg/m2,子宫肌瘤会增加不同水平的PPH风险.母亲吸烟会增加>1500gPPH的风险(调整后的比值比:3.09,95%置信区间[CI]:1.16-8.20)。多元线性分析显示,高龄孕产妇(B:83g;95%CI:27-139g),ART妊娠(B:239g;95%CI:121-357g),孕前BMI为25.0-29.9kg/m2(B:74g;95%CI:22-167g),子宫肌瘤(B:151g;95%CI:47-256g),吸烟(B:107克;95%CI:13-200克),出生体重>3,500g(B:203g;95%CI:67-338g)与计划CS期间失血相关。考虑患者的临床特征可能有助于预测计划CSs中的出血,并有助于提高患者的安全性。
    Given Japan\'s unique social background, it is critical to understand the current risk factors for postpartum hemorrhage (PPH) to effectively manage the condition, especially among specific groups. Therefore, this study aimed to identify the current risk factors for PPH during planned cesarean section (CS) in Japan. This multicenter retrospective cohort study was conducted in two tertiary maternal-fetal medicine units in Fukushima, Japan and included 1,069 women who underwent planned CS between January 1, 2013, and December 31, 2022. Risk factors for PPH (of > 1000 g and > 1500 g) were assessed using multivariate logistic regression analysis, considering variables such as maternal age, parity, assisted reproductive technology (ART) pregnancy, pre-pregnancy body mass index (BMI), uterine myoma, placenta previa, gestational age at delivery, birth weight categories, and hypertensive disorders of pregnancy (HDP). Multivariate linear regression analyses were conducted to predict estimated blood loss during planned CS. ART pregnancy, a pre-pregnancy BMI of 25.0-29.9 kg/m2, and uterine myoma increased PPH risk at various levels. Maternal smoking increased the risk of >1500 g PPH (adjusted odds ratio: 3.09, 95% confidence interval [CI]: 1.16-8.20). Multivariate linear analysis showed that advanced maternal age (B: 83 g; 95% CI: 27-139 g), ART pregnancy (B: 239 g; 95% CI: 121-357 g), pre-pregnancy BMI of 25.0-29.9 kg/m2 (B: 74 g; 95% CI: 22-167 g), uterine myoma (B: 151 g; 95% CI: 47-256 g), smoking (B: 107 g; 95% CI: 13-200 g), and birth weight > 3,500 g (B: 203 g; 95% CI: 67-338 g) were associated with blood loss during planned CS. Considering a patient\'s clinical characteristic may help predict bleeding in planned CSs and help improve patient safety.
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  • 文章类型: Journal Article
    撒哈拉以南非洲地区妊娠期糖尿病(GDM)的疾病负担一直在上升。对GDM当前患病率的正确评估可能会为政策变更和管理方法提供信息,以改善护理服务。
    为了确定当前妊娠糖尿病(GDM)的患病率并评估其在Makurdi孕妇中的主要危险因素,尼日利亚中北部。
    这是一项基于多中心医院的前瞻性观察性研究。对281例孕龄9~16周孕妇的GDM的母体特征和临床危险因素进行了评估。在妊娠24至28周进行一步75g口服葡萄糖耐量试验(OGTT)。
    在被招募的356名女性中,281人(79.8%)完成研究。队列中GDM的患病率为16.7%。孕早期BMI升高(校正后OR=1.154,95%CI=1.080-1.233,p<0.001)和有糖尿病家族史(校正后OR=0.482,95%CI=0.233-0.997,P<0.05)是GDM的独立危险因素。
    在其他可能的原因中,增加产妇年龄和怀孕早期BMI,可能是该地区GDM患病率上升的原因。
    UNASSIGNED: The disease burden of gestational diabetes mellitus (GDM) in sub-Saharan African region have been on the rise. Proper assessment of current prevalence of GDM may inform policy changes and management approach for improved care delivery.
    UNASSIGNED: To determine the current prevalence of Gestational Diabetes Mellitus (GDM) and evaluate its major risk factors amongst pregnant women in Makurdi, North-Central Nigeria.
    UNASSIGNED: This was a multi-center hospital-based prospective observational study. Maternal characteristics and clinical risk factors for GDM in a cohort of 281 pregnant women at 9 to 16 weeks gestational age was evaluated. The one-step 75g oral glucose tolerance test (OGTT) was carried out at 24 to 28 weeks of gestation.
    UNASSIGNED: Of the 356 women recruited, 281 (79.8%) completed the study. The GDM prevalence in the cohort was 16.7%. Increased early pregnancy BMI (adjusted OR = 1.154, 95% CI = 1.080 - 1.233, p<0.001) and presence of family history of diabetes mellitus (adjusted OR = 0.482, 95% CI = 0.233 - 0.997, P<0.05) were independent risk factors for GDM in the cohort.
    UNASSIGNED: Increasing maternal age and early pregnancy BMI amongst other possible reasons, may account for the rising prevalence of GDM in the region.
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  • 文章类型: Journal Article
    描述出生缺陷(包括广泛的特定缺陷)的胎儿死亡率,并探讨出生缺陷导致的胎儿死亡与广泛的人口统计学特征之间的关系。数据来自湖南省出生缺陷监测系统,中国,2016-2020。胎儿死亡是指胎儿在怀孕期间的任何时候在子宫内死亡,包括医疗终止妊娠。胎儿死亡率是指特定群体中每100例出生的胎儿死亡人数(包括活产和胎儿死亡)(单位:%)。采用对数二项式法计算95%置信区间(CI)的出生缺陷胎儿死亡率。计算粗比值比(ORs)以检查每个人口统计学特征与出生缺陷造成的胎儿死亡之间的关系。这项研究包括847,755名新生儿,和23,420出生缺陷被确定。共有11955例胎儿因出生缺陷死亡,胎儿死亡率为51.05%(95%CI50.13-51.96)。15.78%(1887例)因出生缺陷而死亡的胎儿在胎龄<20周,59.05%(7059例)的胎龄为20-27周,胎龄≥28周的占25.17%(3009例)。女性出生缺陷胎儿死亡率高于男性(OR=1.25,95%CI1.18-1.32),农村地区比城市地区(OR=1.43,95%CI1.36-1.50),在20-24岁的产妇中(OR=1.35,95%CI1.25-1.47),与25-29岁的产妇相比,≥35岁(OR=1.19,95%CI1.11-1.29),通过染色体分析诊断比超声(OR=6.24,95%CI5.15-7.55),多胎婴儿低于单胎婴儿(OR=0.41,95%CI0.36-0.47)。出生缺陷的胎儿死亡率随既往妊娠次数的增加而增加(χ2趋势=49.28,P<0.01)。并随既往分娩次数的增加而减少(χ2趋势=4318.91,P<0.01)。许多胎儿死亡与出生缺陷有关。我们发现了一些与出生缺陷胎儿死亡相关的人口统计学特征,这可能与出生缺陷的严重程度有关,经济和医疗条件,和父母对出生缺陷的态度。
    To describe the fetal death rate of birth defects (including a broad range of specific defects) and to explore the relationship between fetal deaths from birth defects and a broad range of demographic characteristics. Data was derived from the birth defects surveillance system in Hunan Province, China, 2016-2020. Fetal death refers to the intrauterine death of a fetus at any time during the pregnancy, including medical termination of pregnancy. Fetal death rate is the number of fetal deaths per 100 births (including live births and fetal deaths) in a specified group (unit: %). The fetal death rate of birth defects with 95% confidence intervals (CI) was calculated by the log-binomial method. Crude odds ratios (ORs) were calculated to examine the relationship between each demographic characteristic and fetal deaths from birth defects. This study included 847,755 births, and 23,420 birth defects were identified. A total of 11,955 fetal deaths from birth defects were identified, with a fetal death rate of 51.05% (95% CI 50.13-51.96). 15.78% (1887 cases) of fetal deaths from birth defects were at a gestational age of < 20 weeks, 59.05% (7059 cases) were at a gestational age of 20-27 weeks, and 25.17% (3009 cases) were at a gestational age of ≥ 28 weeks. Fetal death rate of birth defects was higher in females than in males (OR = 1.25, 95% CI 1.18-1.32), in rural than in urban areas (OR = 1.43, 95% CI 1.36-1.50), in maternal age 20-24 years (OR = 1.35, 95% CI 1.25-1.47), and ≥ 35 years (OR = 1.19, 95% CI 1.11-1.29) compared to maternal age of 25-29 years, in diagnosed by chromosomal analysis than ultrasound (OR = 6.24, 95% CI 5.15-7.55), and lower in multiple births than in singletons (OR = 0.41, 95% CI 0.36-0.47). The fetal death rate of birth defects increased with the number of previous pregnancies (χ2trend = 49.28, P < 0.01), and decreased with the number of previous deliveries (χ2trend = 4318.91, P < 0.01). Many fetal deaths were associated with birth defects. We found several demographic characteristics associated with fetal deaths from birth defects, which may be related to the severity of the birth defects, economic and medical conditions, and parental attitudes toward birth defects.
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  • 文章类型: Journal Article
    众所周知,生殖时的母亲年龄会影响后代的寿命和其他一些与健康相关的特征,但是母体衰老是否会影响后代对环境的反应,目前仍未得到充分研究。早期环境通常在动物行为表型的发展中起重要作用。例如,复杂的环境可以促进幼年动物认知能力和大脑形态的变化。这里,我们研究母体效应衰老是否以及如何影响后代的认知可塑性,群体行为,和大脑形态对环境复杂性的反应。为此,来自年轻和年老母亲(即1岁和2岁)的幼年三头棘鱼暴露于不同程度的环境富集和复杂性(即没有,简单,和复杂),和他们的行为,认知能力,并测量了大脑的大小。将鱼类暴露于丰富的条件下,可以通过重复的弯路任务来评估个人的学习能力,增加了整个大脑的大小,并减少了浅滩中的侵略性相互作用。母亲年龄不影响抑制控制,学习能力,以及后代对实验环境变化的群体行为反应。然而,母亲的年龄会影响后代的某些大脑区域对环境复杂性的反应。在老母亲的后代中,那些暴露于复杂环境的人比那些经历简单环境的人有更大的端脑和小脑。我们的结果表明,母体效应衰老可能会影响后代如何根据环境复杂性投资与认知相关的大脑功能。
    It is well known that maternal age at reproduction affects offspring lifespan and some other fitness-related traits, but it remains understudied whether maternal senescence affects how offspring respond to their environments. Early environment often plays a significant role in the development of an animal\'s behavioral phenotype. For example, complex environments can promote changes in cognitive ability and brain morphology in young animals. Here, we study whether and how maternal effect senescence influences offspring plasticity in cognition, group behavior, and brain morphology in response to environmental complexity. For this, juvenile 3-spined sticklebacks from young and old mothers (i.e. 1-yr and 2-yr-old) were exposed to different levels of environmental enrichment and complexity (i.e. none, simple, and complex), and their behavior, cognitive ability, and brain size were measured. Exposing fish to enriched conditions improved individual learning ability assessed by a repeated detour-reaching task, increased the size of the whole brain, and decreased aggressive interactions in the shoal. Maternal age did not influence the inhibitory control, learning ability, and group behavioral responses of offspring to the experimental environmental change. However, maternal age affected how some brain regions of offspring changed in response to environmental complexity. In offspring from old mothers, those exposed to the complex environment had larger telencephalons and cerebellums than those who experienced simpler environments. Our results suggest that maternal effect senescence may influence how offspring invest in brain functions related to cognition in response to environmental complexity.
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  • 文章类型: English Abstract
    女性生育率随着女性年龄的增加而逐渐下降。其根本原因包括卵母细胞数量和质量的下降。卵母细胞老化是卵母细胞质量下降的重要表现,包括排卵前体内卵母细胞老化和排卵后体外卵母细胞老化。目前,很少有研究来检查卵母细胞的衰老,和相关的分子机制尚未完全了解。因此,我们使用斑马鱼作为研究卵母细胞衰老的模型。选择三种不同年龄范围的雌性斑马鱼与最佳繁殖年龄的雄性斑马鱼交配。这样,我们研究了母亲年龄相关的卵母细胞老化对生育能力的影响,并探讨了母亲年龄相关的生育能力下降的潜在分子机制.
    随机选择年龄在158至195d之间的8条雌性斑马鱼作为6月龄(180±12)d组,随机选取年龄在330~395d的雌性斑马鱼8只作为12月龄组(360±22)d,随机选择年龄在502至583d之间的8只雌性斑马鱼作为18月龄组(540±26)d。从年龄在158至195d之间的斑马鱼中随机选择(180±29)d的雄性斑马鱼,并与雌性斑马鱼交配。每个交配实验包括1只雌性斑马鱼和1只雄性斑马鱼。收集并计数通过交配实验产生的斑马鱼胚胎。在显微镜下观察受精后4小时的胚胎,计算胚胎总数和未受精胚胎的数量,并据此计算了受精率。受精后24小时计数畸形胚胎和死亡胚胎的数量,并据此计算胚胎畸形率和死亡率。主要结局指标是胚胎受精率,次要结果指标是每个产卵的胚胎数(斑马鱼开始交配和繁殖后1.5小时内产下的胚胎总数),胚胎死亡率,和胚胎畸形率。比较各组的结局指标。收集各组雌性斑马鱼在最佳繁殖期与雄性斑马鱼交配后出生的囊胚进行转录组学分析。收集各组雌性斑马鱼的新鲜卵母细胞进行转录组学分析,以探讨母亲年龄相关生育力下降的潜在分子机制。
    与6个月组(94.9%±3.6%)相比,12个月组胚胎受精率(92.3%±4.2%)差异无统计学意义,但18个月组(86.8%±5.5%)显着降低(P<0.01)。此外,18个月组受精率明显低于12个月组(P<0.05)。与6个月组相比,12个月组和18个月组雌性斑马鱼的胚胎死亡率明显高于6个月组(P<0.0001,P<0.001)。三组之间每个菌种的胚胎数量或胚胎畸形率没有显着差异。囊胚胚胎的转录组学分析结果表明,包括dusp5,bdnf,ppip5k2,dgkg,aldh3a2a,acsl1a,哈尔,毛,etc,与6个月组的表达水平相比,在12个月组或18个月组中差异表达。根据KEGG富集分析,这些差异表达基因(DEGs)在MAPK信号通路中显著富集,磷脂酰肌醇信号系统,脂肪酸降解和组氨酸代谢途径(P<0.05)。三组间差异表达基因的表达趋势分析(6个月组,12个月组,反过来,18个月组)显示,fancc的基因表达趋势,Fancg,Fancb,和telo2,涉及范可尼贫血途径,有统计学意义(P<0.05)。在卵母细胞转录组学分析的结果中,与6个月组相比,12个月组或18个月组差异表达的基因主要富集在细胞粘附分子和蛋白质消化吸收途径(P<0.05)。三组斑马鱼卵母细胞基因表达变化趋势的结果(6个月组,12个月组,18个月组)显示,随着母亲年龄的增长,生育力下降的三种基因表达趋势具有显着差异(P<0.05)。进一步分析三种显著差异表达趋势,结果显示51个DEGs与线粒体相关,5个DEGs与端粒维持和DNA修复相关,包括tomm40,mpc2,nbn,tti1等.
    随着斑马鱼母亲年龄的增加,胚胎受精率显著下降,胚胎死亡率显著上升。此外,随着斑马鱼母亲年龄的增加,线粒体和端粒相关基因的表达,如tomm40,mpc2,nbn,和tti1,在雌性斑马鱼卵母细胞中逐渐减少。母亲年龄可能是导致卵母细胞受精能力下降和早期胚胎死亡率增加的因素。母亲年龄相关的卵母细胞老化影响后代的生育能力和胚胎发育。
    UNASSIGNED: Female fertility gradually decreases with the increase in women\'s age. The underlying reasons include the decline in the quantity and quality of oocytes. Oocyte aging is an important manifestation of the decline in oocyte quality, including in vivo oocyte aging before ovulation and in vitro oocyte aging after ovulation. Currently, few studies have been done to examine oocyte aging, and the relevant molecular mechanisms are not fully understood. Therefore, we used zebrafish as a model to investigate oocyte aging. Three different age ranges of female zebrafish were selected to mate with male zebrafish of the best breeding age. In this way, we studied the effects of maternal age-related oocyte aging on fertility and investigated the potential molecular mechanisms behind maternal age-related fertility decline.
    UNASSIGNED: Eight female zebrafish aged between 158 and 195 d were randomly selected for the 6-month age group (180±12) d, 8 female zebrafish aged between 330 and 395 d were randomly selected for the 12-month age group (360±22) d, and 8 female zebrafish aged between 502 and 583 d were randomly selected for the 18-month age group (540±26) d. Male zebrafish of (180±29) d were randomly selected from zebrafish aged between 158 and 195 d and mated with female zebrafish in each group. Each mating experiment included 1 female zebrafish and 1 male zebrafish. Zebrafish embryos produced by the mating experiments were collected and counted. The embryos at 4 hours post-fertilization were observed under the microscope, the total number of embryos and the number of unfertilized embryos were counted, and the fertilization rate was calculated accordingly. The numbers of malformed embryos and dead embryos were counted 24 hours after fertilization, and the rates of embryo malformation and mortality were calculated accordingly. The primary outcome measure was the embryo fertilization rate, and the secondary outcome measures were the number of embryos per spawn (the total number of embryos laid within 1.5 hours after the beginning of mating and reproduction of the zebrafish), embryo mortality, and embryo malformation rate. The outcome measures of each group were compared. The blastocyst embryos of female zebrafish from each group born after mating with male zebrafish in their best breeding period were collected for transcriptomics analysis. Fresh oocytes of female zebrafish in each group were collected for transcriptomics analysis to explore the potential molecular mechanisms of maternal age-related fertility decline.
    UNASSIGNED: Compared with that of the 6-month group (94.9%±3.6%), the embryo fertilization rate of the 12-month group (92.3%±4.2%) showed no significant difference, but that of the 18-month group (86.8%±5.5%) decreased significantly (P<0.01). In addition, the fertilization rate in the 18-month group was significantly lower than that in the 12-month group (P<0.05). Compared with that of the 6-month group, the embryo mortality of the female zebrafish in the 12-month group and that in the 18-month group were significantly higher than that in the 6-month group (P<0.000 1, P<0.001). There was no significant difference in the number of embryos per spawn or in the embryo malformation rate among the three groups. The results of the transcriptomics analysis of blastocyst embryos showed that some genes, including dusp5, bdnf, ppip5k2, dgkg, aldh3a2a, acsl1a, hal, mao, etc, were differentially expressed in the 12-month group or the 18-month group compared with their expression levels in the 6-month group. According to the KEGG enrichment analysis, these differentially expressed genes (DEGs) were significantly enriched in the MAPK signaling pathway, the phosphatidylinositol signaling system, and the fatty acid degradation and histidine metabolism pathway (P<0.05). The analysis of the expression trends of the genes expressed differentially among the three groups (the 6-month group, the 12-month group, and the 18-month group in turn) showed that the gene expression trends of fancc, fancg, fancb, and telo2, which were involved in Fanconi anemia pathway, were statistically significant (P<0.05). In the results of oocyte transcriptomics analysis, the genes that were differentially expressed in the 12-month group or the 18-month group compared with the 6-month group were mainly enriched in cell adhesion molecules and the protein digestion and absorption pathway (P<0.05). The results of the trends of gene expression in the zebrafish oocytes of the three groups (the 6-month group, the 12-month group, and the 18-month group in turn) showed that three kinds of gene expression trends of declining fertility with growing maternal age had significant differences (P<0.05). Further analysis of the three significantly differential expression trends showed 51 DEGs related to mitochondria and 5 DEGs related to telomere maintenance and DNA repair, including tomm40, mpc2, nbn, tti1, etc.
    UNASSIGNED: With the increase in the maternal age of the zebrafish, the embryo fertilization rate decreased significantly and the embryo mortality increased significantly. In addition, with the increase in the maternal age of the zebrafish, the expression of mitochondria and telomere-related genes, such as tomm40, mpc2, nbn, and tti1, in female zebrafish oocytes decreased gradually. Maternal age may be a factor contributing to the decrease in oocyte fertilization ability and the increase in early embryo mortality. Maternal age-related oocyte aging affects the fertility and embryo development of the offspring.
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  • 文章类型: English Abstract
    复发性妊娠丢失(RPL)对接受体外受精-胚胎移植(IVF-ET)的个体提出了巨大的挑战,形成了临床困境和科学探究的焦点。本研究致力于探讨临床特征之间的复杂相互作用,比如年龄,体重指数(BMI),和腰臀比(WHR),和常规实验室参数,包括性激素,血液成分,肝脏和甲状腺功能,甲状腺抗体,和凝血指标,在接受IVF-ET的RPL患者中。通过仔细分析这些变量,我们的目标是揭示潜在的风险因素,使个体发生RPL。确定潜在因素,如高龄产妇,肥胖,和胰岛素抵抗将为临床医生提供重要的见解和经验证据,以加强旨在减少流产复发的预防策略。
    这项回顾性病例对照研究包括在孙逸仙纪念医院接受IVF-ET治疗的RPL患者,中山大学,2012年1月至2021年3月作为病例队列,与因男性不育而接受辅助生殖治疗的女性作为对照队列进行比较。在末次流产后至少12周,首次月经周期前5天收集空腹外周血。比较两组患者的临床特征及相关实验室指标。采用单变量和多变量逻辑回归分析,我们试图挖掘RPL潜在的高危因素.此外,采用线性趋势分析评估总睾酮(TT)水平与流产次数之间的线性关系.
    与对照组相比,RPL队列显示年龄显著增加,BMI,WHR(P<0.05)。值得注意的是,TT水平在RPL队列中明显较低(P=0.022),而两组在基础卵泡刺激素方面没有观察到显著差异,黄体生成素,雌二醇,黄体酮,催乳素水平,和抗苗勒管激素水平(P>0.05)。此外,RPL队列中空腹胰岛素(FINS)水平和HOMA-IR指数明显高于对照组(P<0.001),尽管空腹血糖水平没有显着差异(P>0.05)。此外,中性粒细胞(NEU)计数和NEU与淋巴细胞的比率在RPL队列中明显更高(P<0.01)。单因素Logistic回归分析确定了几个因素,包括年龄≥35岁,BMI≥25kg/m2,WHR>0.8,FINS>10mU/L,HOMA-IR>2.14,NEU计数>6.3×109L-1,NEU/淋巴细胞比值(NLR)升高,显著增加RPL的风险(P<0.05)。尽管两个队列的TT水平都在正常范围内,较高的TT水平与RPL风险降低相关(比值比[OR]=0.67,95%置信区间[CI]:0.510-0.890,P=0.005).在对混杂因素进行调整后,年龄≥35岁(OR=1.91,95%CI:1.06-3.43),WHR>0.8(OR=2.30,95%CI:1.26-4.19),FINS>10mU/L(OR=4.50,95%CI:1.30-15.56)是RPL的有效危险因素(P<0.05)。相反,较高的TT水平与RPL风险降低相关(OR=0.59,95%CI:0.38-0.93,P=0.023).此外,线性趋势分析揭示了TT水平与流产次数之间的明显线性关系(P趋势=0.003),表明随着流产事件的升级,TT水平呈下降趋势。
    在接受IVF-ET的患者中,高龄产妇,较低的TT水平,WHR增加,和升高的FINS水平成为RPL的有效危险因素。这些发现为临床医生提供了宝贵的见解,并有助于识别高风险患者并制定预防策略以减少流产的复发。
    UNASSIGNED: Recurrent pregnancy loss (RPL) presents a formidable challenge for individuals undergoing in vitro fertilization-embryo transfer (IVF-ET), forming both a clinical dilemma and a focal point for scientific inquiry. This study endeavors to investigate the intricate interplay between clinical features, such as age, body mass index (BMI), and waist-to-hip ratio (WHR), and routine laboratory parameters, including sex hormones, blood composition, liver and thyroid functions, thyroid antibodies, and coagulation indicators, in RPL patients undergoing IVF-ET. By meticulously analyzing these variables, we aim to uncover the latent risk factors predisposing individuals to RPL. Identifying potential factors such as advanced maternal age, obesity, and insulin resistance will provide clinicians with vital insights and empirical evidence to strengthen preventive strategies aimed at reducing miscarriage recurrence.
    UNASSIGNED: This retrospective case-controlled study included RPL patients who underwent IVF-ET treatment at Sun Yat-sen Memorial Hospital, Sun Yat-sen University, between January 2012 and March 2021 as the case cohort, compared with women receiving assisted reproductive treatment due to male infertility as the control cohort. The fasting peripheral blood was collected 5 days before the first menstrual cycle at least 12 weeks after the last abortion. The clinical characteristics and relevant laboratory indexes of the two groups were compared. Employing both univariate and multivariate logistic regression analyses, we sought to unearth potential high-risk factors underlying RPL. Additionally, a linear trend analysis was conducted to assess the linear relationship between total testosterone (TT) levels and the number of miscarriages.
    UNASSIGNED: In contrast to the control cohort, the RPL cohort exhibited significant increases in age, BMI, and WHR (P<0.05). Notably, TT levels were markedly lower in the RPL cohort (P=0.022), while no significant differences were observed between the two groups concerning basal follicle-stimulating hormone, luteinizing hormone, estradiol, progesterone, prolactin levels, and anti-Müllerian hormone levels (P>0.05). Moreover, fasting insulin (FINS) levels and HOMA-IR index were notably elevated in the RPL cohort relative to the control cohort (P<0.001), although no significant differences were observed in fasting blood glucose levels (P>0.05). Furthermore, the neutrophil (NEU) count and NEU-to-lymphocyte ratio were notably higher in the RPL cohort (P<0.01). Univariate logistic regression analysis identified several factors, including age≥35 years old, BMI≥25 kg/m2, WHR>0.8, FINS>10 mU/L, HOMA-IR>2.14, NEU count>6.3×109 L-1, and an elevated NEU/lymphocyte ratio (NLR), as significantly increasing the risk of RPL (P<0.05). Although TT levels were within the normal range for both cohorts, higher TT levels were associated with a diminished RPL risk (odds ratio [OR]=0.67, 95% confidence interval [CI]: 0.510-0.890, P=0.005). After adjustments for confounding factors, age≥35 years old (OR=1.91, 95% CI: 1.06-3.43), WHR>0.8 (OR=2.30, 95% CI: 1.26-4.19), and FINS>10 mU/L (OR=4.50, 95% CI: 1.30-15.56) emerged as potent risk factors for RPL (P<0.05). Conversely, higher TT levels were associated with a reduced RPL risk (OR=0.59, 95% CI: 0.38-0.93, P=0.023). Furthermore, the linear trend analysis unveiled a discernible linear association between TT levels and the number of miscarriages (P trend=0.003), indicating a declining trend in TT levels with escalating miscarriage occurrences.
    UNASSIGNED: In patients undergoing IVF-ET, advanced maternal age, lower TT levels, increased WHR, and elevated FINS levels emerged as potent risk factors for RPL. These findings provide clinicians with valuable insights and facilitate the identification of patients who are at high risks and the formulation of preventive strategies to reduce the recurrence of miscarriages.
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