雌激素浓度与人工周期冻融胚胎移植患者妊娠结局的关系.pdf
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1、67Jul.22023Chinese Journal of Woman and Child Health Research2023年7 月Vol.34No.7中国妇幼健康研究第34卷第7 期雌激素浓度与人工周期冻融胚胎移植患者妊娠结局的关系樊艳玲,樊月?,丰程文,刘宝莲1(1.唐山市妇幼保健院生殖医学中心,河北唐山0 6 30 0 0;2.华北理工大学,河北唐山0 6 30 0 0)【摘要目的分析雌激素浓度与人工周期冻融胚胎移植(FET)患者妊娠结局的关系。方法纳入2 0 2 0 年2 月至2 0 2 1年1月在唐山市妇幼保健院生殖医学中心接受FET助孕的8 0 0 例不孕症患者为研究对象,所
2、有患者均在内膜转化日常规检测卵泡刺激素(FSH)、黄体生成素(LH)、抗苗勒氏管激素(AMH)、孕酮(P)、雌二醇(E2),并于移植前1天测量子宫内膜厚度。根据移植后第35d超声检查结果评估患者妊娠成功率,将患者分为临床妊娠组和未妊娠组;对临床妊娠组展开随访,以随访期间孕妇、胎儿及新生儿不良事件评估妊娠结局,将其分为不良结局和良好结局。构建Logistic回归模型,分析雌激素浓度与人工周期FET患者临床妊娠率及妊娠结局的关系。结果果8 0 0 例不孕症患者均完成人工周期FET,在接受35d观察后,共有36 0 例患者确认为临床妊娠,临床妊娠率为45.0 0%;未妊娠440 例,占55.0 0%
3、。与未妊娠组相比,临床妊娠组患者年龄较小,内膜转化日血清P、E2 浓度较高,移植日内膜较厚,差异均有统计学意义(Z/t值分别为11.36 0、2.391、19.7 6 7、13.8 12,P0.05)。Lo g i s t i c 回归分析显示,年龄、E2浓度、移植日内膜厚度与人工周期FET患者临床妊娠率有关,OR及其95%CI值分别为1.32 9(1.2 431.42 1)、0.959(0.9 52 0.9 6 5)、0.30 9(0.2 350.40 8),P 0.0 5。348 例临床妊娠患者完成随访,期间共18 6 例有不良妊娠结局,占53.45%;16 2 例妊娠结局良好,占46.5
4、5%。与良好妊娠结局患者相比,不良妊娠结局患者年龄普遍较大,内膜转化日血清E2浓度较低,移植日内膜厚度较小,差异均有统计学意义(Z/t值分别为5.513、9.0 8 6、7.2 11,P0.05)。Lo g i s t i c 回归分析显示,年龄、E2浓度、移植日内膜厚度与人工周期FET患者妊娠结局有关,OR及其95%CI值分别为1.2 58(1.1511.37 5)、0.96 9(0.96 10.978)、0.348(0.2 42 0.50 0),P 0.0 5。结论内膜转化日E2浓度与人工周期FET患者临床妊娠率及妊娠结局均有关,E2浓度降低可增加妊娠失败的风险,不利于胚胎发育,甚至影响妊
5、娠结局。关键词不孕症;人工周期;冻融胚胎移植;雌激素;妊娠结局Doi:10.3969/j.issn.1673-5293.2023.07.010中图分类号 R173文献标识码 A文章编号16 7 352 93(2 0 2 3)0 7 0 0 6 7 0 7Relationship between estrogen concentration and pregnancy outcome in patientswith artificial cycle frozen-thawed embryo transferFAN Yanling,FAN Yue?,FENG Chengwen,LIU Baolia
6、n(l1.Reproductive Medicine Center,Tangshan Maternal and Child Health Hospital,Hebei Tangshan 063000,China;2.North China University of Science and Technology,Hebei Tangshan 063000,China)Abstract Objective To analyze the relationship between estrogen concentration and pregnancy outcome in patients wit
7、h artificialcycle frozen-thawed embryo transfer(FET).Methods A total of 80o infertile patients who received FET assisted pregnancy in re-productive medicine center of Tangshan Maternal and Child Health Hospital from February 2020 to January 2021 were included asthe study subjects.Follicle-stimulatin
8、g hormone(FSH),luteinizing hormone(LH),anti-Mullerian hormone(AMH),progesterone(P),and estradiol(E,)were routinely detected on the day of endometrial transformation in all patients,and measured endometrialthickness 1 day before transplantation.The success rate of pregnancy was evaluated according to
9、 the results of ultrasound examina-tion on the 35th day after transplantation,and the patients were divided into clinical pregnancy group and non-pregnancy group.Theclinical pregnancy group was followed up,and the pregnancy outcome was evaluated by adverse events of pregnant women,fetusesand neonate
10、s during the follow-up period,which were divided into adverse outcomes and good outcomes.Logistic regression modelwas established to analyze the relationship between estrogen concentration and clinical pregnancy rate and pregnancy outcome in pa-tients with artificial cycle FET.Results Among the 800
11、infertility patients,all completed artificial cycle FET.After 35d observa-收稿日期2 0 2 2 0 9 0 8基金项目2 0 2 2 年度河北省医学科学研究课题(2 0 2 2 17 6 7)作者简介樊艳玲(198 8 一),女,主治医师,硕士研究生,主要从事人类辅助生育的研究。通讯作者刘宝莲,主任医师。68在线投稿网址tion,a total of 360 patients were confirmed to be clinically pregnant,with a clinical pregnancy rate
12、of 45.00%.There were 440 caseswithout pregnancy,accounting for 55.00%.Compared with the non-pregnancy group,the patients in the clinical pregnancy groupwere generally younger,the serum P and Ez concentrations on the day of endometrial transformation were higher,and the endome-trium on the day of tra
13、nsplantation was thicker,and the differences were statistically significant(Z/t=11.360,2.391,19.767 and13.812,respectively,P0.05).Logistic regression analysis showed that age,E2 concentration and intimal thickness on the day oftransplantation were related to the clinical pregnancy rate of patients w
14、ith artificial cycle FET,the OR values and 95%CI were1.329(1.243-1.421),0.959(0.952-0.965)and 0.309(0.235-0.408),respectively,P0.05.348 c l i n i c a l p r e g n a n c y p a t i e n t s c o m-pleted follow-up,during which 186 cases had adverse pregnancy outcomes,accounting for 53.45%.162 cases had g
15、ood pregnancyoutcomes,accounting for 46.55%.Compared with the patients with good pregnancy outcome,the patients with adverse pregnancyoutcomes were generally older,the serum Ez concentration on the day of endometrial transformation was lower,and the intimathickness on the day of transplantation was
16、smaller,the differences were statistically significant(Z/t=5.513,9.086 and 7.211,re-spectively,P0.05).Logistic regression analysis showed that age,E2 concentration on the day of endometrial transformation,andendometrial thickness on the day of transplantation were related to the pregnancy outcome of
17、 patients with artificial cycle FET,theOR values and 95%CI were 1.258(1.151-1.375),0.969(0.961-0.978)and 0.348(0.242-0.500),respectively,P 18 岁;由同一临床医师进行FET;胚胎冷冻方法为玻璃化冷冻,冷冻胚胎均为卵裂期胚胎;首次接受FET,同意接受激素替代方案进行胚胎移植;均使用配偶精液进行体外受精,夫妻双方染色核型均正常;卵泡刺激素(follicule-stimulatinghormone,FSH)1oU/L。排除标准:卵巢、子宫器质性病变;既往有卵巢、
18、子宫手术史;患有盆腔炎、阴道炎等妇科炎症疾病;卵巢、子宫形态学改变;近3个月服用过抗凝药等可能影响子宫血流的药物;近3个月服用激素类药物者;测量过程中子宫内膜与肌层边界不清晰,影响内膜厚度测量结果。剔除标准:对研究药物过敏需终止用药;胚胎移植后未完成随访;因其他因素导致妊娠失败,如外界因素、药物因素等。本研究经过医院伦理委员会审核通过(2 0 2 1一0 32 一0 1),患者及家属均自愿签署知情同意书。69Jul.20232023年7 月Chinese Journal of Woman and Child Health ResearchVol.34No.7第34卷第7 期中国妇幼健康研究1.
19、2研究方法1.2.1内膜准备在月经来潮或药物撤退性出血第3天接受超声检查,观察子宫和卵巢。若无明显异常,开始服用戊酸雌二醇片(补佳乐,DELPHARMLilleS.A.S.国药准字J20171038,规格:1mg21片)4mg/d,服用7天后再次接受超声检查,测量子宫内膜厚度。若子宫内膜厚度7 mm则维持上述剂量继续服用;若子宫内膜厚度7mm则进行内膜转化,若仍未达标准者则继续增加补佳乐剂量至8 mg/d,最大剂量不超过10 mg/d。内膜转化:第1天,肌肉注射黄体酮注射液(国药准字H12020533,规格:2 0 mg)40 m g/d 十口服地屈孕酮片(A b b o t t Bi o l
20、 o g i c a l s B.V.,批准文号:H20170221规格:10 mg)2 0 mg/d;第2 天,肌肉注射黄体酮注射液6 0 mg/d+口服地屈孕酮片2 0 mg/d;第34天,肌肉注射黄体酮注射液8 0 mg/d(上午、下午各40mg)十服用地屈孕酮片2 0 mg/d,同时维持补佳乐使用剂量;第5天进行D3卵裂期胚胎移植。移植后黄体支持方法:雌激素用法用量不变,服用地屈孕酮片2 0 mg/d,肌肉注射黄体酮注射液,移植第1天注射40 mg,第2 天注射6 0 mg,第34天8 0 mg。1.2.2血液指标检测内膜转化日(移植前1天)常规抽血3mL检测患者激素浓度,检测项目包括
21、血清FSH、黄体生成素(l u t e i n i z i n g h o r mo n e,LH)、抗苗勒氏管激素(anti-Mullerian hormone,AMH)、孕酮(progesterone,P)、雌二醇(estradiol,E,)浓度。离心速率为350 0 r/min,离心时间为10 min,检测方法为化学发光法,试剂盒购自上海酶联生物科技有限公司。1.3妊娠结局评估临床妊娠:胚胎移植后第14天进行血绒毛膜促性腺激素(human chorionic gonadotropin,hCG)检测,以hCG高于正常值(正常值为 10 mIU/mL),且移植后第35天时超声可见宫内妊娠囊视
22、为临床妊娠,否则视为未妊娠。妊娠结局:对临床妊娠者展开随访,直至完成分娩。不良妊娠结局定义为随访期间发生孕妇、胎儿及新生儿不良事件,如流产、早产、胎儿生长受限(fetal growthrestriction,FG R)、新生儿室息等。1.4临床资料分别统计临床妊娠和未妊娠两组及不同妊娠结局患者的一般临床资料,包括年龄、体质量指数(b o d y ma s s i n d e x,BM I)、不孕年限、不孕原因、平均周期数,以及内膜转化日血清FSH、LH、E2、P、AMH浓度和移植日内膜厚度。1.5统计学方法应用SPSS25.0软件进行数据处理和分析,计数资料使用频数(n)和百分比(%)表示,组
23、间比较采用x检验;计量资料经Shapiro-Wilk正态分布检验,若符合正态分布则使用均数和标准差(x士s)表示,组间比较使用独立样本t检验,若为偏态分布则使用中位数和四分位数间距M(P2 5,P7 s)表示,组间比较使用非参数MannWhitneyU检验。采用Logistic回归分析雌激素浓度与人工周期FET患者临床妊娠率及妊娠结局的关系,P0.05表示差异有统计学意义。2结果2.1FET患者的临床妊娠率本研究纳人的8 0 0 例不孕症患者均完成人工周期FET。在接受35天观察后,共有36 0 例患者确认为临床妊娠,临床妊娠率为45.0 0%(36 0/8 0 0);未妊娠者440 例,占5
24、5.0 0%(440/8 0 0),其中宫外孕5例,占1.14%(5/440)。2.2临床妊娠患者与未妊娠患者一般资料的比较临床妊娠组患者年龄小于未妊娠组,内膜转化日血清P、E,浓度高于未妊娠组,移植日内膜厚度大于未妊娠组,上述差异均有统计学意义(Z/t值分别为11.36 0、2.39 1、19.7 6 7、13.8 12,P0.05),见表1。2.3雌激素浓度与人工周期FET患者临床妊娠的关系以人工周期FET患者临床妊娠情况为因变量(临床妊娠=0,未妊娠=1),以年龄、P、E2、移植日内膜厚度为自变量,构建Logistic回归模型。结果显示,年龄(OR=1.329,95%CI:1.2431.
25、42 1)、E2 浓度(OR=0.959,95%C I:0.952 0.96 5)、移植日子宫内膜厚度(OR=0.309,95%CI:0.2 350.40 8)与70在线投稿网址httpna.11-人工周期FET患者临床妊娠率有关,见表2。芯有油不灶派平牛表1临床妊娠患者与未妊娠患者一般资料的比较n(%),x士s,M(P25,Prs)Table 1 Comparison of general data between clinical pregnant patients and non-pregnant patients n(%),Xs,M(P25,Prs)一般资料临床妊娠组(n=360)未妊
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- 雌激素 浓度 人工 周期 胚胎 移植 患者 妊娠 结局 关系