中国全科医学 ›› 2023, Vol. 26 ›› Issue (02): 160-167.DOI: 10.12114/j.issn.1007-9572.2022.0397

• 论著 • 上一篇    下一篇

胚胎种植前遗传学检测助孕妊娠结局的影响因素研究

王博雅1,2,3,4, 何英明1,2,3,4, 薛吟霜2,3,4,5, 向卉芬1,2,3,4,5,*()   

  1. 1230011 安徽省合肥市,安徽医科大学第四附属医院妇产科
    2230022 安徽省合肥市,国家卫生健康委配子及生殖道异常研究重点实验室
    3230022 安徽省合肥市,出生人口健康教育部重点实验室
    4230022 安徽省合肥市,生殖健康与遗传安徽省重点实验室
    5230022 安徽省合肥市,安徽医科大学第一附属医院妇产科
  • 收稿日期:2022-03-15 修回日期:2022-07-25 出版日期:2023-01-15 发布日期:2022-08-25
  • 通讯作者: 向卉芬
  • 王博雅,何英明,薛吟霜,等.胚胎种植前遗传学检测助孕妊娠结局的影响因素研究[J].中国全科医学,2023,26(2):160-167.[www.chinagp.net]
    作者贡献:王博雅负责文章的构思、研究的设计、撰写论文;王博雅、何英明、薛吟霜负责文献、患者资料的收集、数据收集与整理;王博雅、何英明进行结果的分析与解释;向卉芬对文章整体负责,负责论文的可行性分析、修订、文章的审查及监督。
  • 基金资助:
    国家自然科学基金资助项目(9021382202)

Factors Associated with the Outcomes of Preimplantation Genetic Testing in Assisted Reproduction

WANG Boya1,2,3,4, HE Yingming1,2,3,4, XUE Yinshuang2,3,4,5, XIANG Huifen1,2,3,4,5,*()   

  1. 1Department of Obstetrics and Gynecology, the Fourth Affiliated Hospital of Anhui Medical University, Hefei 230011, China
    2NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei 230022, China
    3Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, Hefei 230022, China
    4Anhui Province Key Laboratory of Reproductive Health and Genetics, Hefei 230022, China
    5Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
  • Received:2022-03-15 Revised:2022-07-25 Published:2023-01-15 Online:2022-08-25
  • Contact: XIANG Huifen
  • About author:
    WANG B Y, HE Y M, XUE Y S, et al. Factors associated with the outcomes of preimplantation genetic testing in assisted reproduction [J] . Chinese General Practice, 2023, 26 (2) : 160-167.

摘要: 背景 育龄期女性胚胎着床失败及流产的最常见原因是胚胎异常,但移植经胚胎种植前遗传学检测(PGT)筛选后的正常胚胎后,仍出现种植失败或流产的原因目前并没有形成统一的结论。 目的 分析PGT助孕后种植失败及流产的影响因素。 方法 回顾性分析2018年12月至2021年2月在安徽医科大学第一附属医院生殖中心行PGT助孕的329例患者的临床资料,根据患者是否临床妊娠分为临床妊娠组(n=218)和种植失败组(n=111),并将临床妊娠组患者根据妊娠结局分为活产亚组(n=175)和流产亚组(n=43)。比较临床妊娠组和种植失败组,活产亚组和流产亚组的一般情况、促排卵及体外胚胎发育情况。采用多因素Logistic回归分析探讨PGT患者种植失败及流产的影响因素。绘制受试者工作特征(ROC)曲线分析多因素Logistic回归分析筛选出的影响因素对PGT患者发生种植失败及流产的预测价值。 结果 多因素Logistic回归分析显示,既往流产次数≥2次〔OR=4.032 0,95%CI(2.423 0,6.710 0)〕、高密度脂蛋白胆固醇(HDL-C)水平低〔OR=3.890 0,95%CI(1.455 0,10.403 0)〕是PGT患者种植失败的危险因素(P<0.05),低促性腺激素(Gn)用量〔OR=0.999 5,95%CI(0.999 2,0.999 9)〕是PGT患者种植失败的保护因素(P<0.05);既往流产次数≥2次〔OR=2.203 0,95%CI(1.099 0,4.417 0)〕、低胚胎活检正常率〔OR=5.655 0,95%CI(1.286 0,24.865 0)〕是PGT患者流产的危险因素(P<0.05),低空腹胰岛素(FINS)水平〔OR=0.912 0,95%CI(0.835 0,0.996 0)〕是PGT患者流产的保护因素(P<0.05)。ROC曲线分析结果显示,既往流产次数≥2次、HDL-C水平、Gn用量预测PGT患者发生种植失败曲线下面积分别为0.650、0.579、0.561,灵敏度分别为70.3%、33.3%、60.4%,特异度分别为59.6%、80.3%、56.9%,约登指数分别为0.299、0.136、0.173;既往流产次数≥2次、FINS水平、胚胎活检正常率预测PGT患者发生流产曲线下面积分别为0.648、0.629、0.641,灵敏度分别为66.2%、72.1%、65.1%,特异度分别为63.4%、52.6%、60.6%,约登指数分别为0.296、0.247、0.257。 结论 既往流产次数≥2次、Gn用量、HDL-C是PGT患者种植失败的影响因素且可预测PGT患者种植失败;既往流产次数≥2次、FINS水平、胚胎活检正常率是PGT患者流产的影响因素且可预测PGT患者流产。

关键词: 植入前诊断, 种植前遗传学检测, 妊娠结局, 活产, 流产, 生殖技术,辅助, 影响因素分析

Abstract:

Background

Embryo anomaly is the most common cause of implantation failure and abortion in women of reproductive age. However, there is controversy about the cause of implantation failure or miscarriage that occurs after the transfer of a normal embryo screened by preimplantation genetic testing (PGT) .

Objective

To analyze the influencing factors affecting implantation failure and miscarriage after PGT assisted reproduction.

Methods

Three hundred and twenty-nine women who received PGT assisted reproduction in Reproductive Center, the First Affiliated Hospital of Anhui Medical University from December 2018 to February 2021 were enrolled, including 218 with clinical pregnancy〔175 of whom had a live birth (live birth subgroup) , and 43 had an abortion (abortion subgroup) 〕, and 111 with implantation failure. Clinical data, results of accessory examinations, ovulation induction and in vitro embryonic development were compared between women with clinical pregnancy and implantation failure, and between live birth and abortion subgroups. The influencing factors of implantation failure and abortion after PGT assisted reproduction were screened by multivariate logistic regression analysis, and predictive values of the determined factors for implantation failure and abortion were estimated using the receiver operating characteristic (ROC) analysis.

Results

Multivariate logistic regression analysis showed that, two or more previous abortions〔OR=4.032 0, 95%CI (2.423 0, 6.710 0) 〕 and low level of high-density lipoprotein cholesterol (HDL-C) 〔OR=3.890 0, 95%CI (1.455 0, 10.403 0) 〕were risk factors for implantation failure after PGT assisted reproduction (P<0.05) , while the low gonadotropin (Gn) dosage〔OR=0.999 5, 95%CI (0.999 2, 0.999 9) 〕 was associated with decreased risk of implantation failure after PGT assisted reproduction (P<0.05) . Two or more abortions〔OR=2.203 0, 95%CI (1.099 0, 4.417 0) 〕 and low normal rate of embryo biopsy〔OR=5.655 0, 95%CI (1.286 0, 24.865 0) 〕 were associated with increased risk of abortion after PGT assisted reproduction (P<0.05) , while low fasting insulin (FINS) level〔OR=0.912 0, 95%CI (0.835 0, 0.996 0) 〕 was associated with decreased risk of abortion after PGT assisted reproduction (P<0.05) . ROC analysis indicated that for predicting implantation failure after PGT assisted reproduction, the AUC of two or more previous abortions was 0.650 with 70.3% sensitivity, 59.6% specificity and Youden index of 0.299, the AUC of HDL-C level was 0.579 with 33.3% sensitivity, 80.3% specificity and Youden index of 0.136, and the AUC of the dosage of Gn was 0.561 with 60.4% sensitivity, 56.9% specificity and Youden index of 0.173. The AUC of two or more previous abortions for predicting the abortion after PGT assisted reproduction was 0.648 with 66.2% sensitivity, 63.4% specificity and Youden index of 0.296, and the AUC of fasting insulin level was 0.629 with 72.1% sensitivity, 52.6% specificity and Youden index of 0.247, and that of normal embryo biopsy rate was 0.641 with 65.1% sensitivity, 60.6% specificity and Youden index of 0.257.

Conclusion

Two or more previous abortions, dosage of Gn and serum HDL-C were influencing factors and partial predictors of implantation failure after PGT assisted reproduction. And two or more previous abortions, fasting insulin level, and normal embryo biopsy rate were influencing factors and partial predictors of abortion after PGT assisted reproduction.

Key words: Preimplantation diagnosis, Preimplantation genetic testing, Pregnancy outcome, Live birth, Miscarriage, Reproductive techniques, assisted, Root cause analysis