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体外受精-胚胎移植与PCOS对子痫前期发病的影响

Effects of in Vitro Fertilization-embryo Transfer and Polycystic Ovary Syndrome on the Incidence of Preeclampsia

【作者】 刘莹

【导师】 王晨虹;

【作者基本信息】 南方医科大学 , 妇产科学(专业学位), 2020, 硕士

【摘要】 子痫前期(PE)是严重威胁母婴生命健康的产科常见并发症。既往研究报道体外受精-胚胎移植(IVF-ET)妊娠后子痫前期发病率增加,尚不能确定是IVF-ET相关技术还是女性自身不孕因素导致子痫前期高风险。多囊卵巢综合征(PCOS)是不孕症的常见原因,PCOS已证实与子痫前期密切相关。PCOS女性通过IVF助孕后子痫前期风险是否进一步增加?PCOS和IVF对子痫前期的发病是否存在交互作用尚不清楚。本研究旨在探讨IVF和PCOS对子痫前期风险的单独和联合影响,为评估辅助生殖技术的安全性提供理论依据及参考。第一章 体外受精-胚胎移植与子痫前期相关性[目的]通过倾向评分匹配的方法研究子痫前期发病率在IVF助孕和自然妊娠中的差异,探讨IVF与子痫前期的相关性。[方法]选取分娩孕周大于24周的孕妇4823例,其中IVF助孕组481例,自然妊娠组4342例。通过倾向评分匹配的方法,得到组间协变量均衡的样本(924例);分别比较匹配前后样本中两组子痫前期发病率及发病特征。[结果]1.匹配前,IVF助孕组的子痫前期发病率高于自然妊娠组(9.8%vs.3.3%,P<0.05),多因素回归分析显示IVF是子痫前期的危险因素(aOR=1.887;95%CI:1.23~2.89,P=0.003);倾向评分匹配后OR 为 2.067(95%CI:1.24~3.44,P=0.005),证实了体外受精-胚胎移植与子痫前期存在显著关联。2.在单胎妊娠中,IVF助孕组子痫前期发生率显著高于自然妊娠(9.0 vs.3.1%,aOR=2.530,95%CI:1.63~3.94,P>0.05);在双胎妊娠中,两组子痫前期发生率没有显著差异(12.7vs.7.5%,aOR=1.004,95%CI:0.35~2.87,P=0.994);与倾向评分匹配样本所得结果一致。3.匹配后两组子痫前期患者的发病孕周、分娩孕周、平均血压、尿蛋白等实验室指标以及母婴不良结局比较无显著差异(P>0.05)。[结论]通过多因素logistic 回归分析和倾向评分匹配分析,得出相同结论:IVF-ET妊娠后子痫前期的发病风险增加,IVF-ET是单胎妊娠发生子痫前期的重要危险因素,IVF-ET并没有显著增加双胎妊娠发生子痫前期的风险。第二章体外受精-胚胎移植与PCOS对子痫前期的交互作用[目的]探讨体外受精-胚胎移植术、PCOS及其交互作用对子痫前期的影响。[方法]选取分娩孕周大于24周的单胎孕妇4154例,统计孕妇基本信息及PE发病情况。应用相加模型、相乘模型分析PCOS、IVF及其交互作用与子痫前期的关系。[结果]控制混杂因素后,多因素回归分析显示:PCOS女性患子痫前期的风险为正常女性的2.47倍,IVF助孕女性患子痫前期风险为自然妊娠者的1.9倍(OR分别为2.470、1.904,P均<0.05)。交互作用分析显示:IVF助孕的PCOS女性患子痫前期的风险是自然妊娠非PCOS女性的4.92倍(aOR=4.918,95%CI:2.31~10.48);两个因素之间没有相加或相乘交互作用[交互作用指标:交互作用指数(S)、超额相对危险度(RERI)、归因比(API)分别为1.81、1.75、35.6%]。[结论]1.PCOS、IVF均是子痫前期的危险因素,PCOS女性通过IVF-ET妊娠后子痫前期风险进一步增加;2.PCOS和IVF的交互作用与子痫前期无统计学关联,体外受精-胚胎移植术和PCOS与子痫前期的风险增加独立相关。

【Abstract】 [Background]Preeclampsia(PE)is a common obstetric complication that seriously threatens the health of mothers and infants.Previous studies have reported an increase in the incidence of preeclampsia after in vitro fertilization-embryo transfer(IVF-ET).It is not yet known whether IVF-ET related technologies or women’s own infertility cause high preeclampsia risk.Polycystic ovary syndrome(PCOS)is a common cause of infertility.PCOS has been shown to be closely related to preeclampsia.Is PCOS Women’s preeclampsia risk further increased after IVF treatment?It is unclear whether PCOS and IVF interact with each other in preeclampsia.The purpose of this study was to explore the individual and combined effects of’ IVF and PCOS on preeclampsia risk,and to provide a theoretical basis and reference for assessing the safety of assisted reproductive technology.Chapter I Correlation between in vitro fertilization-embryo transfer and preeclampsia[Objective]The difference in the incidence of preeclampsia between IVF pregnancy and natural pregnancy was studied by the propensity score matching method,to explore the correlation between IVF pregnancy and preeclampsia.[Method]A total of 4,823 pregnant women with a gestational age greater than 24 weeks were selected,including 481 in the IVF group and 4342 in the natural pregnancy group.By the method of propensity score matching,samples with balanced covariates among the groups(924 cases)were obtained;the incidence and characteristics of preeclampsia in the two groups were compared before and after matching.[Result]1.Before matching,the incidence of preeclampsia in the IVF group was higher than that in the natural pregnancy group(9.8%vs.3.3%,P<0.05).Multivariate regression analysis showed that IVF was a risk factor for preeclampsia(aOR=1.887;95%Cl:1.23~2.89,P=0.003);After matching propensity score OR was 2.067(95%CI:1.24~3.44,P=0.005),confirming the existence of IVF and preeclampsia Significantly related.2.In single pregnancy,the risk of preeclampsia in the IVF group is significantly higher than natural pregnancy(9.0vs.3.1%,aOR=2.530,95%CI:1.63~3.94,P<0.05);in twin pregnancy,There was no significant difference in the risk of preeclampsia between the IVF group and the natural pregnancy group(12.7vs.7.5%,aOR=1.004,95%CI:0.35~2.87,P=0.994);the results were consistent with those obtained by matching the propensity score sample.3.There were no significant differences in laboratory indicators such as gestational week,gestational week,mean blood pressure,urine protein,and maternal-infant outcome between the two groups of preeclampsia patients after propensity score matching(P>0.05).[Conclusion]Multivariate logistic regression analysis and propensity score matching analysis,reached the same conclusion:IVF pregnancy increases the risk of preeclampsia.IVF-ET is an important risk factor for preeclampsia in single pregnancy.IVF-ET does not significantly increase the risk of preeclampsia in twin pregnancyChapter II Interaction between in vitro fertilization-embryo transfer and PCOS on preeclampsia[Objective]To investigate the effects of in vitro fertilization-embryo transfer、PCOS and their interactions on preeclampsia[Method]A total of 4154 singleton pregnant women with a gestational age greater than 24 weeks were selected to calculate the basic information of pregnant women and the incidence of PE.The relationship between PCOS,IVF and their interactions with preeclampsia was analyzed using the addition model and multiplication model[Result]After controlling for confounding factors,multivariate regression analysis showed that the risk of preeclampsia in women with PCOS was 2.47 times that of normal women,and the risk of preeclampsia in women with IVF pregnancy was 1.9 times that of natural pregnancy(P<0.05).Interaction analysis showed that PCOS women with IVF-ET pregnancy had a pre-eclampsia risk of 4.92 times than that of natural non-PCOS women(aOR=4.918,95%CI:2.31~10.48);there was no addition or multiplication interaction between the two factors[Interaction index:Synergy Index(S)、Relative excess risk of interaction(RERI)、and Attributable proportion(AP)were 1.81、1.75、35.6%].[Conclusion]1.PCOS and IVF are risk factors for preeclampsia.PCOS women have a higher risk of preeclampsia after IVF pregnancy2.The interaction between PCOS and IVF is not statistically related to preeclampsia.IVF and PCOS are independently associated with increased risk of preeclampsia.

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