Emma Children's Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Paediatrics, Department of Gynaecology and Obstetrics, Amsterdam Reproduction and Development Research Institute, Amsterdam Public Health Research Institute, De Boelelaan 1117, P.O. Box 7057, 1007 MB Amsterdam, the Netherlands; NYC Health and Hospitals/Lincoln, Department of Pediatrics, Room 4-20, 234 East 149(th) Street, Bronx, NY, 10451, United States.
Amsterdam UMC, University of Amsterdam, Department of Obstetrics and Gynaecology, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam Reproduction and Development Research Institute, Amsterdam Public Health Research Institute, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
Eur J Obstet Gynecol Reprod Biol. 2019 Nov;242:131-138. doi: 10.1016/j.ejogrb.2019.09.026. Epub 2019 Sep 26.
Does ovarian hyperstimulation and/or the in vitro procedure of assisted reproduction affect neurodevelopmental and physical health of the offspring?
Infertile couples were randomly allocated to intrauterine insemination with controlled ovarian hyperstimulation (IUI-COH), modified natural cycle in vitro fertilization (IVF-MNC) or single embryo transfer IVF (IVF-SET). We compared neurodevelopmental and physical health in childhood (4-7 years). We used age-appropriate questionnaires to assess behavioral problems (Child Behavior Check List (CBCL)) and executive functioning (Behavior Rating Inventory of Executive Function (BRIEF)). We measured body mass index Z-score, waist- and hip-circumference, body fat percentage, blood pressure Z-scores, pulse wave velocity, glucose, insulin, insulin resistance, total cholesterol, high- and low-density lipoprotein cholesterol, triglycerides, and high sensitivity c-reactive protein. We compared groups by analysis of variance.
We examined 191 (57%) of the 333 children born in the study at a mean age of 5.5 years (range 4.0-7.6 years). We found no statistically significant differences between randomization groups in children's neurodevelopmental or physical health indices (all p-values > 0.05). Comparing the outcomes between actual method of conception, including a naturally conceived group, also did not show statistically significant differences.
Although this follow-up study was not powered on childhood outcomes and limited power due to attrition may have hampered detection of subtle effects, we found no indications of differences in neurodevelopmental and physical health between ovarian hyperstimulation and/or the in vitro procedure of assisted reproduction. Future trials should be powered on child outcomes, and aim to optimize follow-up rates to provide answers that are more definitive.
卵巢刺激和/或辅助生殖的体外程序是否会影响后代的神经发育和身体健康？
不孕夫妇被随机分配到宫腔内人工授精加控制性卵巢刺激（IUI-COH）、改良自然周期体外受精（IVF-MNC）或单胚胎移植体外受精（IVF-SET）。我们比较了儿童期（4-7 岁）的神经发育和身体健康。我们使用适合年龄的问卷评估行为问题（儿童行为检查表（CBCL））和执行功能（行为评定量表的执行功能（BRIEF））。我们测量了体重指数 Z 评分、腰围和臀围、体脂百分比、血压 Z 评分、脉搏波速度、血糖、胰岛素、胰岛素抵抗、总胆固醇、高低密度脂蛋白胆固醇、甘油三酯和高敏 C 反应蛋白。我们通过方差分析比较了各组。
我们在研究中检查了 191 名（57%）出生于该研究的 333 名儿童，平均年龄为 5.5 岁（范围 4.0-7.6 岁）。我们发现随机分组的儿童神经发育或身体健康指数之间没有统计学上的显著差异（所有 p 值均>0.05）。将实际受孕方法（包括自然受孕组）的结果进行比较，也没有显示出统计学上的显著差异。
尽管这项随访研究在儿童结局方面没有足够的效力，由于失访可能会阻碍对细微影响的检测，因此效力有限，但我们没有发现卵巢刺激和/或辅助生殖的体外程序在神经发育和身体健康方面存在差异的迹象。未来的试验应该在儿童结局上有足够的效力，并旨在优化随访率，以提供更明确的答案。
