Mizrak I, Asserhøj L L, Lund M A V, Kielstrup L R, Greisen G, Clausen T D, Main K M, Jensen R B, Vejlstrup N G, Madsen P L, Pinborg A
Department of Cardiology, Copenhagen University Hospital, Herlev-Gentofte, Herlev, Denmark.
Fertility Department, Copenhagen University Hospital, Rigshospitalet, Denmark, Copenhagen.
Hum Reprod. 2022 Mar 1;37(3):600-611. doi: 10.1093/humrep/deab284.
Do 8- to 9-year-old singletons conceived after frozen embryo transfer (FET) or fresh embryo transfer (Fresh-ET) have increased arterial stiffness compared to naturally conceived (NC) children?
The process of FET or Fresh-ET is not associated with altered cardiovascular function in 8- to 9-year-old singletons, including arterial stiffness, as compared to NC children.
ART has been suggested to influence cardiovascular risk factors (i.e. endothelial dysfunction, increased arterial blood pressure and insulin resistance). It is not known if ART procedures alter arterial stiffness in singletons.
STUDY DESIGN, SIZE, DURATION: A cohort study was carried out, including 8- to 9-year-old singletons conceived after FET, Fresh-ET and NC children (50 children in each group). This study was conducted between November 2018 and August 2020.
PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 150 singletons were identified through the Danish IVF Registry and the Medical Birth Registry. They underwent cardiac magnetic resonance imaging (CMR) and anthropometric measurements. Parental data were collected using questionnaires. NC children were matched by sex and birth year with FET/Fresh-ET children. Exclusion criteria were congenital heart disease, maternal gestational diabetes or maternal diabetes mellitus. Our primary outcome was arterial stiffness, which is assessed from noninvasive arterial blood pressure and aortic ascendens distensibility. The secondary outcome was the pulse wave velocity of total aorta and exploratory outcomes were left ventricular ejection fraction, mean arterial pressure, cardiac output and total peripheral resistance. Measurements and analyses were performed blinded to the child group.
Aortic ascendens distensibility of children conceived after FET and Fresh-ET did not differ from NC children (mean (SD): FET 11.1 (3.6) 10-3 mmHg-1, Fresh-ET 11.8 (3.0) 10-3 mmHg-1, NC 11.4 (2.8) 10-3 mmHg-1, P > 0.05). Multivariate linear regression was performed to adjust for potential confounders (i.e. child sex and age, maternal BMI at early pregnancy and maternal educational level). Data showed no statistically significant differences between study groups and aortic ascendens distensibility. However, the fully adjusted model showed a non-significant tendency of lowered aortic ascendens distensibility in children born after FET compared to Fresh-ET (β estimate (95% CI): -0.99 10-3 mmHg-1 (-2.20; 0.21)) and NC children (β estimate (95% CI): -0.77 10-3 mmHg-1 (-1.98; 0.44)). Lastly, secondary and exploratory outcomes did not differ between the groups. Primary and secondary outcomes showed good intra-rater reliability.
LIMITATIONS, REASONS FOR CAUTION: This study is possibly limited by potential selection bias as the participation rate was higher in the ART compared to the NC group. Also, in some variables, the study groups differed slightly from the non-participant population. The non-participant population (n = 1770) included those who were excluded, not invited to CMR scan, or declined to participate in this study.
Our findings indicate that children born after FET or Fresh-ET do not have altered cardiovascular function, including arterial stiffness. This is reassuring for the future use of ART.
STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Novo Nordisk Foundation (grant reference number: NNF19OC0054340) and The Research Foundation of Rigshospitalet. All authors declared no conflict of interests.
ClinicalTrials.gov identifier: NCT03719703.
与自然受孕（NC）的儿童相比，冻融胚胎移植（FET）或新鲜胚胎移植（Fresh-ET）后出生的8至9岁单胎儿童的动脉僵硬度是否增加？
与NC儿童相比，FET或Fresh-ET过程与8至9岁单胎儿童的心血管功能改变无关，包括动脉僵硬度。
有研究表明辅助生殖技术（ART）会影响心血管危险因素（即内皮功能障碍、动脉血压升高和胰岛素抵抗）。但尚不清楚ART程序是否会改变单胎儿童的动脉僵硬度。
研究设计、规模、持续时间：进行了一项队列研究，纳入FET、Fresh-ET后出生的8至9岁单胎儿童以及NC儿童（每组50名儿童）。该研究于2018年11月至2020年8月期间进行。
参与者/材料、设置、方法：通过丹麦体外受精登记处和医疗出生登记处共识别出150名单胎儿童。他们接受了心脏磁共振成像（CMR）和人体测量。通过问卷收集父母的数据。NC儿童按性别和出生年份与FET/Fresh-ET儿童进行匹配。排除标准为先天性心脏病、母亲妊娠期糖尿病或母亲糖尿病。我们的主要结局是动脉僵硬度，通过无创动脉血压和升主动脉扩张性进行评估。次要结局是总主动脉脉搏波速度，探索性结局是左心室射血分数、平均动脉压、心输出量和总外周阻力。测量和分析对儿童分组情况设盲。
FET和Fresh-ET后出生儿童的升主动脉扩张性与NC儿童无差异（均值（标准差）：FET 11.1（3.6）×10⁻³ mmHg⁻¹，Fresh-ET 11.8（3.0）×10⁻³ mmHg⁻¹，NC 11.4（2.8）×10⁻³ mmHg⁻¹，P>0.05）。进行多变量线性回归以调整潜在混杂因素（即儿童性别和年龄、孕早期母亲体重指数和母亲教育水平）。数据显示研究组之间升主动脉扩张性无统计学显著差异。然而，完全调整模型显示，与Fresh-ET后出生儿童相比，FET后出生儿童的升主动脉扩张性有降低的非显著趋势（β估计值（95%置信区间）：-0.99×10⁻³ mmHg⁻¹（-2.20；0.21）），与NC儿童相比也有降低的非显著趋势（β估计值（95%置信区间）：-0.77×10⁻³ mmHg⁻¹（-1.98；0.44））。最后，次要和探索性结局在各组之间无差异。主要和次要结局显示出良好的评分者内信度。
局限性、谨慎理由：本研究可能受潜在选择偏倚的限制，因为ART组的参与率高于NC组。此外，在一些变量上，研究组与未参与者人群略有不同。未参与者人群（n = 1770）包括被排除者、未被邀请进行CMR扫描者或拒绝参与本研究者。
我们的研究结果表明，FET或Fresh-ET后出生的儿童心血管功能未改变，包括动脉僵硬度。这为ART的未来应用提供了安心的依据。
研究资金/利益冲突：本研究由诺和诺德基金会（资助编号：NNF19OC0054340）和里格霍斯医院研究基金会资助。所有作者均声明无利益冲突。
ClinicalTrials.gov标识符：NCT03719703。
