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曹亚聪, 李一鸣, 潘萍, 等. 体外受精-胚胎移植患者中反复妊娠丢失的危险因素分析[J]. koko体育app 学报(医学版), 2024, 55(3): 724-730. DOI:
引用本文: 曹亚聪, 李一鸣, 潘萍, 等. 体外受精-胚胎移植患者中反复妊娠丢失的危险因素分析[J]. koko体育app 学报(医学版), 2024, 55(3): 724-730. DOI:
CAO Yacong, LI Yiming, PAN Ping, et al. Analysis of Risk Factors for Recurrent Pregnancy Loss in Patients Undergoing in vitro Fertilization-Embryo Transfer[J]. Journal of Sichuan University (Medical Sciences), 2024, 55(3): 724-730. DOI:
Citation: CAO Yacong, LI Yiming, PAN Ping, et al. Analysis of Risk Factors for Recurrent Pregnancy Loss in Patients Undergoing in vitro Fertilization-Embryo Transferꩲ[J]. Journal of Sichuan University (Medical Sciences), 2024, 55(3): 724-730. DOI:

体外受精-胚胎移植患者中反复妊娠丢失的危险因素分析

Analysis of Risk Factors for Recurrent Pregnancy Loss in Patients Undergoing in vitro Fertilization-Embryo Transfer

  • 摘要:
    目的 探讨体外受精-胚胎移植(in vitro fertilization-embryo transfer, IVF-ET)患者发生反复妊娠丢失(recurrent pregnancy loss, RPL)的危险因素。
    方法 本研究采用回顾性病例对照设计,纳入2012年1月–2021年3月在中山大学孙逸仙纪念医院进行IVF-ET的反复妊娠丢失患者作为病例组,因男性不育而行IVF-ET治疗的妇女为对照组。在最后一次流产后至少12周的首次月经周期前5 d采集患者空腹外周血,比较两组的临床特征及实验室相关指标,并采用单因素和多因素logistic回归模型分析可能影响RPL的潜在高危因素。采用线性趋势检验确定总睾酮(total testosterone, TT)水平与流产次数间的线性关系。
    结果 与对照组相比,RPL组的年龄、体重指数及腰臀比(waist-to-hip ratio, WHR)均增加,差异有统计学意义(P<0.05)。RPL组的TT水平较对照组降低(P=0.022),两组间基础卵泡刺激素、黄体生成素、雌二醇、孕酮、泌乳素水平及抗米勒管激素水平差异无统计学意义(P>0.05)。与对照组相比,RPL组的空腹胰岛素(fasting insulin, FINS)水平及胰岛素抵抗指数的稳态评估模型升高(P<0.001),两组间空腹血糖水平差异无统计学意义(P>0.05)。RPL组的中性粒细胞计数及中性粒细胞/淋巴细胞比值水平较对照组升高(P<0.01)。在调整其他因素后,年龄≥35岁〔比值比(odds ratio, OR)=1.91,95%置信区间(confidence interval, CI):1.06~3.43〕、WHR>0.8(OR=2.30,95%CI:1.26~4.19)、FINS>10 mU/L(OR=4.50,95%CI:1.30~15.56)会增加RPL的风险(P<0.05)。TT水平的升高会降低RPL的发病风险(OR=0.59,95%CI:0.38~0.93,P=0.023)。线性趋势检验发现,TT与自然流产次数间存在线性相关关系(Ptrend=0.003)。
    结论 在接受IVF-ET的患者中,高龄、TT水平的降低、WHR升高及FINS水平升高是RPL的危险因素。
     
    Abstract:
    Objective 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.
    Methods 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.
    Results 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 (Ptrend=0.003), indicating a declining trend in TT levels with escalating miscarriage occurrences.
    Conclusion 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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