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9 岁试管婴儿后代的心血管健康:与卵巢过度刺激和体外程序无关。

Cardiovascular health of 9-year-old IVF offspring: no association with ovarian hyperstimulation and the in vitro procedure.

机构信息

University of Groningen, University Medical Center Groningen, Department of Pediatrics, Division Developmental Neurology, Hanzeplein 1, Groningen GZ 9713, The Netherlands.

University of Groningen, University Medical Center Groningen, Department of Obstetrics and Gynaecology, Hanzeplein 1, Groningen GZ 9713, The Netherlands.

出版信息

Hum Reprod. 2017 Dec 1;32(12):2540-2548. doi: 10.1093/humrep/dex323.

DOI:10.1093/humrep/dex323
PMID:29087467
Abstract

STUDY QUESTION

Are the in vitro procedure, ovarian hyperstimulation or a combination of these two associated with blood pressure (BP) of 9-year-old IVF children born to subfertile couples?

SUMMARY ANSWER

Our study demonstrates that ovarian hyperstimulation and the in vitro procedure are not associated with BP values in 9-year-old children born to subfertile couples.

WHAT IS KNOWN ALREADY

Possible long-term effects of IVF on child health and development have been studied relatively little. This is surprising, as it is known that environmental conditions may influence embryonic and foetal development which may result in health related problems in later life. Some studies suggested that IVF is associated with higher BP at pre-school age. Yet, it is unclear whether this may be also true for older children and if so, which component of IVF, i.e. the ovarian hyperstimulation, the embryo culture or a combination of these, attributes to this potentially less favourable BP.

STUDY DESIGN, SIZE, DURATION: The Groningen Assisted Reproductive Technology cohort-study is a prospective assessor-blinded study of children followed from before birth onwards. In total, 170 children were assessed at the age of 9 years. The attrition rate up until the 9-year-old assessment was 21%.

PARTICIPANTS/MATERIALS, SETTING, METHODS: We evaluated cardiovascular health, focusing on BP (in mmHg and the internationally recognized percentiles of the US National High BP Education Program), heart rate and anthropometrics of 57 children born following controlled ovarian hyperstimulation-IVF/ICSI (COH-IVF/ICSI); 47 children born after modified natural cycle-IVF/ICSI (MNC-IVF/ICSI); and 66 children who were conceived naturally by subfertile couples (Sub-NC). Cardiovascular parameters were measured multiple times on one day. In addition, anthropometric data, including BMI and skinfold thickness, were collected.

MAIN RESULTS AND THE ROLE OF CHANCE

Systolic BP in mmHg did not differ between the COH-IVF/ICSI (mean 106.9, SD 6.7), MNC-IVF/ICSI (mean 104.8, SD 5.9) and Sub-NC (mean 106.3, SD 5.3) groups. In addition, systolic BP percentiles did not differ between the groups: COH-IVF/ICSI (mean 62.4, SD 20.2); MNC-IVF/ICSI (mean 56.3, SD 19.3); and Sub-NC (mean 62.3, SD17.8). Also, after adjustment for confounders BP in the three groups was similar. Heart rate and anthropometric values in the three groups did not differ. For instance, BMI values in the COH-IVF/ICSI-children were 16.3 (median value, range 13.0-24.7), in MNC-IVF/ICSI-children 16.1 (range 12.7-22.5) and in Sub-NC children 16.3 (range 12.7-24.0).

LIMITATIONS, REASONS FOR CAUTION: The size of our study groups does not allow for pertinent conclusions on the effect of ovarian hyperstimulation and the in vitro procedure. The lack of a fertile control group may be regarded as another limitation.

WIDER IMPLICATIONS OF THE FINDINGS

Our study suggests that ovarian hyperstimulation and in vitro procedures are not associated with cardiovascular health in 9-year-old. Yet, BP percentiles of the three groups were higher than the expected 50th percentile. This might indicate that children of subfertile couples have a higher BP than naturally conceived children.

STUDY FUNDING/COMPETING INTEREST(S): The study was financially supported by the University Medical Center Groningen (UMCG), the two graduate schools of the UMCG, BCN, SHARE and the Cornelia Stichting. The sponsors of the study had no role in study design, data collection, data analysis, data interpretation or writing of the report. The authors have no conflicts of interest to declare.

摘要

研究问题

体外程序、卵巢过度刺激或两者的结合与不孕夫妇所生的 9 岁试管婴儿的血压(BP)有关吗?

总结答案

我们的研究表明,卵巢过度刺激和体外程序与不孕夫妇所生 9 岁儿童的 BP 值无关。

已知情况

体外受精对儿童健康和发育的长期影响相对较少。这令人惊讶,因为已知环境条件可能会影响胚胎和胎儿的发育,这可能导致以后生活中的健康问题。一些研究表明,体外受精与学龄前儿童的血压升高有关。然而,目前尚不清楚这是否也适用于年龄较大的儿童,如果是这样,体外受精的哪个组成部分,即卵巢过度刺激、胚胎培养或两者的结合,会导致这种潜在的血压升高。

研究设计、规模、持续时间:格罗宁根辅助生殖技术队列研究是一项前瞻性评估者盲法研究,从出生前开始对儿童进行评估。共有 170 名儿童在 9 岁时接受了评估。截至 9 岁评估时,失访率为 21%。

参与者/材料、设置、方法:我们评估了心血管健康,重点是血压(以 mmHg 和美国国家高血压教育计划的国际公认百分位数表示)、心率和 57 名接受控制性卵巢过度刺激-体外受精/卵胞浆内单精子注射(COH-IVF/ICSI)的儿童的人体测量学;47 名接受改良自然周期-IVF/ICSI(MNC-IVF/ICSI)的儿童;以及 66 名自然受孕的不孕夫妇(Sub-NC)的儿童。在一天内多次测量心血管参数。此外,还收集了人体测量学数据,包括 BMI 和皮褶厚度。

主要结果和机会的作用

以 mmHg 计的收缩压在 COH-IVF/ICSI(平均 106.9,SD 6.7)、MNC-IVF/ICSI(平均 104.8,SD 5.9)和 Sub-NC(平均 106.3,SD 5.3)组之间没有差异。此外,各组的收缩压百分位数也没有差异:COH-IVF/ICSI(平均 62.4,SD 20.2);MNC-IVF/ICSI(平均 56.3,SD 19.3);Sub-NC(平均 62.3,SD17.8)。此外,在调整混杂因素后,三组的血压相似。三组的心率和人体测量值没有差异。例如,COH-IVF/ICSI 组的 BMI 值为 16.3(中位数,范围 13.0-24.7),MNC-IVF/ICSI 组为 16.1(范围 12.7-22.5),Sub-NC 组为 16.3(范围 12.7-24.0)。

局限性、谨慎的原因:我们的研究小组规模不大,无法得出关于卵巢过度刺激和体外程序影响的相关结论。缺乏正常生育对照组可能是另一个限制。

研究结果的更广泛意义

我们的研究表明,卵巢过度刺激和体外程序与 9 岁儿童的心血管健康无关。然而,三组的 BP 百分位数均高于预期的第 50 百分位数。这可能表明不孕夫妇的孩子的血压比自然受孕的孩子高。

研究资金/利益冲突:该研究得到格罗宁根大学医学中心(UMCG)、UMCG 的两个研究生院、BCN、SHARE 和 Cornelia 基金会的支持。该研究的赞助商在研究设计、数据收集、数据分析、数据解释或报告撰写方面没有任何作用。作者没有利益冲突要声明。

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