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胚胎植入前非整倍体基因检测(PGT-A)对孕早期生化标志物——妊娠相关血浆蛋白A(PAPP-A)和游离β-人绒毛膜促性腺激素(β-hCG)的影响。

Impact of preimplantation genetic testing for aneuploidies (PGT-A) on first trimester biochemical markers - PAPP-A (placenta-associated plasma protein) and free β-hCG (human chorionic gonadotropin).

作者信息

Markova D, Kagan O, Hoopmann M, Abele H, Coughlan C, Abecia E, Fatemi H M, Lawrenz B

机构信息

Fetal Medicine Unit, ART Fertility Clinics, Abu Dhabi, United Arab Emirates.

Department of Feto-Maternal Medicine, Women's University Hospital Tuebingen, Tuebingen, Germany.

出版信息

J Matern Fetal Neonatal Med. 2022 Dec;35(25):6097-6103. doi: 10.1080/14767058.2021.1906857. Epub 2021 Apr 6.

Abstract

OBJECTIVE

The objective of the study was to study the effect of preimplantation genetic testing for aneuploidies (PGT-A) performed at blastocyst stage on the levels of first trimester biomarkers.

METHODS

This is an observational, collaborative, retrospective study. Seven hundred and twenty-eight patients were included in the study. Patients were with singleton pregnancies resulting from either natural conception (NC), or assisted reproductive techniques (ARTs) with PGT-A and frozen embryo transfer (FET) (ART/PGT-A/FET) or after ART without PGT-A and fresh ET (ART/no PGT-A/fresh ET) or FET (ART/no PGT-A/FET), who had first trimester combined screening test between 11 and 14 gestational weeks. They were stratified into four groups: group A (ART/PGT-A/FET) - 143 patients; group B (ART/no PGT-A/FET) - 100 patients; group C (ART/no PGT-A/fresh ET) - 346 patients, and group D (NC) - 139 patients.

RESULTS

Statistically significant differences among the examined groups were observed for maternal age, BMI, ethnicity, and parity. The median placenta-associated plasma protein (PAPP-A) was lowest in the group with ART/PGT-A/FET and the highest result was obtained in the group with ART/no PGT-A/FET. Statistically significant difference in the median PAPP-A levels was identified among the examined groups ( = .0186). When a subgroup analysis was performed, a statistically significant difference was observed in the median PAPP-A between ART/PGT-A/FET group versus ART/no PGT-A/FET group ( = .01) and NC versus ART/no PGT-A/FET ( = .01). A similar trend toward statistical significance was noted when comparing NC versus ART/no PGT-A/fresh ET ( = .06). Multivariate analysis elucidated that when age is present in the model, the effect of any method of conception or testing for aneuploidy disappears. The other factors (BMI, ethnicity, and parity) do not influence the levels of PAPP-A. The lowest median free human chorionic gonadotropin (β-HCG) was recorded in the NC group and the highest result was identified in the group with IVF/PGT-A/FET. No statistically significant difference was observed in the median concentration levels of free β-hCG among the compared groups ( = .5789) and when subgroup analysis was performed (>.05). The normality of the distribution of variables was analyzed by the Kolmogorov-Smirnov test and the median PAPP-A and free βhCG concentration difference by the Wilcoxon rank-sum test with nonparametric ANOVA.

CONCLUSIONS

Testing for aneuploidy (PGT-A) and the decision to transfer either fresh or cryopreserved embryos (ET) appear not to affect the levels of first trimester biochemical markers. The findings of the present study should be a baseline for future studies and could be used to improve the antenatal screening counseling for women with ART pregnancies and PGT-A.

摘要

目的

本研究的目的是探讨囊胚期非整倍体植入前基因检测(PGT-A)对孕早期生物标志物水平的影响。

方法

这是一项观察性、协作性、回顾性研究。研究纳入了728例患者。患者为单胎妊娠,其受孕方式包括自然受孕(NC)、采用PGT-A和冷冻胚胎移植(FET)的辅助生殖技术(ART)(ART/PGT-A/FET)、未采用PGT-A的ART及新鲜胚胎移植(ART/no PGT-A/fresh ET)或FET(ART/no PGT-A/FET),且在孕11至14周进行了孕早期联合筛查。他们被分为四组:A组(ART/PGT-A/FET)-143例患者;B组(ART/no PGT-A/FET)-100例患者;C组(ART/no PGT-A/fresh ET)-346例患者;D组(NC)-139例患者。

结果

在研究组之间观察到产妇年龄、体重指数、种族和胎次存在统计学显著差异。胎盘相关血浆蛋白(PAPP-A)中位数在ART/PGT-A/FET组中最低,在ART/no PGT-A/FET组中最高。在研究组之间确定了PAPP-A中位数水平的统计学显著差异(P = 0.0186)。进行亚组分析时,在ART/PGT-A/FET组与ART/no PGT-A/FET组之间观察到PAPP-A中位数存在统计学显著差异(P = 0.01),在NC组与ART/no PGT-A/FET组之间也存在统计学显著差异(P = 0.01)。在比较NC组与ART/no PGT-A/fresh ET组时也注意到类似的统计学显著趋势(P = 0.06)。多变量分析表明,当年龄纳入模型时,任何受孕方式或非整倍体检测方法的影响均消失。其他因素(体重指数、种族和胎次)不影响PAPP-A水平。游离人绒毛膜促性腺激素(β-HCG)中位数在NC组中最低,在IVF/PGT-A/FET组中最高。在比较组之间未观察到游离β-HCG中位数浓度水平的统计学显著差异(P = 0.5789),进行亚组分析时也未观察到显著差异(P>0.05)。通过Kolmogorov-Smirnov检验分析变量分布的正态性,通过非参数方差分析的Wilcoxon秩和检验分析PAPP-A中位数和游离βhCG浓度差异。

结论

非整倍体检测(PGT-A)以及移植新鲜或冷冻胚胎(ET)的决定似乎不影响孕早期生化标志物水平。本研究结果应作为未来研究的基线,并可用于改善对ART妊娠和PGT-A妇女的产前筛查咨询。

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