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受孕前母体心血管风险状况会影响体外受精/卵胞浆内单精子注射妊娠中的人类胚胎生长轨迹。

The periconception maternal cardiovascular risk profile influences human embryonic growth trajectories in IVF/ICSI pregnancies.

作者信息

Wijnands K P J, van Uitert E M, Roeters van Lennep J E, Koning A H J, Mulders A G M G J, Laven J S E, Steegers E A P, Steegers-Theunissen R P M

机构信息

Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre, PO Box 2040, Rotterdam 3000CA, The Netherlands.

Department of Internal Medicine, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands.

出版信息

Hum Reprod. 2016 Jun;31(6):1173-81. doi: 10.1093/humrep/dew060. Epub 2016 Apr 15.

Abstract

STUDY QUESTION

Is the maternal cardiovascular (CV) risk profile associated with human embryonic growth trajectories and does the mode of conception affect this association?

SUMMARY ANSWER

This small study suggests that the maternal CV risk profile is inversely associated with first trimester embryonic growth trajectories in in vitro fertilization (IVF)/intra-cytoplasmic sperm injection (ICSI) pregnancies, but not in spontaneously conceived pregnancies.

WHAT IS KNOWN ALREADY

Maternal high-blood pressure and smoking affect placental function, accompanied by increased risk of fetal growth restriction and low-birthweight. Mothers who experience pregnancies complicated by fetal growth restriction are at increased risk of CV disease in later life.

STUDY DESIGN, SIZE, DURATION: In a prospective periconception birth cohort conducted in a tertiary hospital, 111 singleton ongoing pregnancies with reliable pregnancy dating, no pre-existing maternal disease and no malformed live borns were investigated.

PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Spontaneously conceived pregnancies with a reliable first day of the last menstrual period and a regular menstrual cycle of 25-31 days only (n = 66) and IVF/ICSI pregnancies (n = 45) were included. Women underwent weekly three-dimensional ultrasound scans (3D US) from 6- to 13-week gestational age. To estimate embryonic growth, serial crown-rump length (CRL) measurements were performed using the V-Scope software in a BARCO I-Space. Maternal characteristics and CV risk factors were collected by self-administered questionnaires. The CV risk profile was created based on a score of risk factors, including maternal age, body-mass index, CV disease in the family, diet and smoking. Quartiles of the CV risk score were calculated. Associations between the CV risk score and embryonic growth were assessed using square root transformed CRL in multivariable linear mixed model analyses.

MAIN RESULTS AND THE ROLE OF CHANCE

From the 111 included pregnancies, 696 3D US data sets were obtained of which 637 (91.5%) CRLs could be measured. In the total group, The CV risk score was inversely, but not significantly associated with embryonic growth (-0.03√mm; P = 0.291). Stratified by mode of conception, the CV risk score was inversely and significantly associated with embryonic growth (β = -0.04√mm; P = 0.025, adjusted for possible confounders) in the IVF/ICSI group. Compared with the first quartile, embryos in the upper quartile were 10.4% smaller at 6(+0) weeks (4.4 versus 4.9 mm) and 3.1% smaller at 12(+0) weeks (56.5 versus 58.4 mm) of gestation. Although the CV risk score was slightly, but significantly, higher in women conceiving spontaneously compared with those undergoing IVF/ICSI treatment [CV risk score = 2.06 (SD: 1.23) and 1.60 (SD: 1.15), respectively], no association was established with embryonic growth in that particular group.

LIMITATIONS, REASONS FOR CAUTION: Participants included in the present cohort are women with a singleton ongoing pregnancy without any pre-existing disease and selected from a tertiary hospital. Hence, they represent a selected group of women. Larger and population-based periconception birth cohort studies are recommended to demonstrate external validity.

WIDER IMPLICATIONS OF THE FINDINGS

Differences in embryonic growth between pregnancies conceived spontaneously and after IVF/ICSI treatment in relation with CV risk factors substantiate the importance of more investigation into differences in sensitivity of endometrial, endothelial, placental and embryonic tissues.

STUDY FUNDING/COMPETING INTERESTS: Funded by the Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands. The authors declare no conflict of interest.

摘要

研究问题

孕产妇心血管(CV)风险状况是否与人类胚胎生长轨迹相关,受孕方式是否会影响这种关联?

简要回答

这项小型研究表明,在体外受精(IVF)/卵胞浆内单精子注射(ICSI)妊娠中,孕产妇CV风险状况与孕早期胚胎生长轨迹呈负相关,但在自然受孕妊娠中并非如此。

已知信息

孕产妇高血压和吸烟会影响胎盘功能,同时胎儿生长受限和低出生体重的风险增加。经历过胎儿生长受限妊娠的母亲在晚年患心血管疾病的风险增加。

研究设计、规模、持续时间:在一家三级医院进行的前瞻性受孕前出生队列研究中,调查了111例单胎持续妊娠,这些妊娠的孕周确定可靠,无孕产妇基础疾病,且出生的活产儿无畸形。

参与者/材料、设置、方法:纳入仅最后一次月经首日可靠且月经周期为25 - 31天规律的自然受孕妊娠(n = 66)和IVF/ICSI妊娠(n = 45)。从孕6周到13周,女性每周接受一次三维超声扫描(3D US)。为评估胚胎生长,使用BARCO I-Space中的V-Scope软件进行连续头臀长(CRL)测量。通过自我填写问卷收集孕产妇特征和CV风险因素。根据包括孕产妇年龄、体重指数、家族心血管疾病、饮食和吸烟等风险因素的评分创建CV风险状况。计算CV风险评分的四分位数。在多变量线性混合模型分析中,使用平方根转换后的CRL评估CV风险评分与胚胎生长之间的关联。

主要结果及偶然性的作用

在纳入的111例妊娠中,获得了696个3D US数据集,其中637个(91.5%)CRL可测量。在整个组中,CV风险评分与胚胎生长呈负相关,但无显著关联(-0.03√mm;P = 0.291)。按受孕方式分层,在IVF/ICSI组中,CV风险评分与胚胎生长呈负相关且具有显著意义(β = -0.04√mm;P = 0.025,对可能的混杂因素进行了校正)。与第一四分位数相比,处于上四分位数的胚胎在妊娠6(+0)周时小10.4%(4.4对4.9 mm),在12(+0)周时小百分之3.1(56.5对58.4 mm)。尽管自然受孕女性的CV风险评分略高于接受IVF/ICSI治疗的女性,但具有显著差异[CV风险评分分别为2.06(标准差:1.23)和1.60(标准差:1.15)],但在该特定组中未发现与胚胎生长的关联。

局限性、谨慎原因:本队列中的参与者是单胎持续妊娠且无任何基础疾病的女性,并且是从一家三级医院选取的。因此,她们代表了一组经过挑选的女性。建议进行更大规模的基于人群的受孕前出生队列研究以证明外部有效性。

研究结果的更广泛影响

自然受孕与IVF/ICSI治疗后妊娠在胚胎生长方面与CV风险因素的差异,证实了进一步研究子宫内膜、内皮、胎盘和胚胎组织敏感性差异的重要性。

研究资金/利益冲突:由荷兰鹿特丹伊拉斯姆斯医学中心大学医学中心妇产科资助。作者声明无利益冲突。

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