Drenth Olivares Machiel, Kuiper Derk B, Haadsma Maaike L, Heineman Kirsten R, Heineman Maas Jan, Hadders-Algra Mijna
University of Groningen, University Medical Center Groningen, Department of Paediatrics, Division Developmental Neurology, Hanzeplein 1, Groningen 9713 GZ, the Netherlands.
University of Groningen, University Medical Center Groningen, Department of Genetics, Hanzeplein 1, Groningen 9713 GZ, the Netherlands.
Early Hum Dev. 2019 Feb;129:38-44. doi: 10.1016/j.earlhumdev.2018.12.017. Epub 2019 Jan 9.
In vitro fertilization (IVF) is not associated with neurological abnormalities in offspring's early childhood. Yet, it is unclear whether this is also true for school age. Neither do we know the role of parental subfertility in offspring's neurological development. The present study examined neurological condition at 9 years of 57 singletons born after controlled ovarian hyperstimulation IVF (COH-IVF), 46 singletons born after modified natural cycle IVF (MNC-IVF) and 66 singletons born to subfertile parents after natural conception (Sub-NC). To assess the effect of subfertility, the groups were pooled to form a subfertile group, and compared with a prospectively followed fertile reference group (n = 282). The sensitive Minor Neurological Dysfunction (MND) examination was used, resulting in the detailed Neurological Optimality Score (NOS) and the prevalence of the clinically relevant complex MND. Neurological condition of the three subfertile groups did not differ significantly: median NOS was 53 in each subfertile group and the prevalence of complex MND in the three subfertile groups was 30%, 37% and 36%, respectively. However, the NOS was lower and the prevalence of complex MND higher in children born to subfertile couples than in children of fertile couples (adjusted mean difference [95% CI]: -4.48 [-5.53 to -3.42]) and adjusted OR [95% CI]: 5.13 [2.60-10.16], respectively). We conclude that ovarian hyperstimulation, in vitro procedures, and the combination of both were not associated with a less favourable neurological outcome of 9-year-old singletons. However, the presence of parental subfertility was associated with less favourable neurological outcome of offspring at 9 years follow up.
体外受精（IVF）与子代幼儿期的神经发育异常并无关联。然而，对于学龄期儿童而言，情况是否依然如此尚不清楚。我们也不清楚父母的生育力低下在子代神经发育中所起的作用。本研究调查了57例经控制性卵巢刺激体外受精（COH-IVF）后出生的单胎、46例经改良自然周期体外受精（MNC-IVF）后出生的单胎以及66例生育力低下的父母自然受孕后出生的单胎在9岁时的神经状况。为评估生育力低下的影响，将这些组合并形成一个生育力低下组，并与一个前瞻性随访的生育对照组（n = 282）进行比较。采用了敏感的轻微神经功能障碍（MND）检查，得出详细的神经优化评分（NOS）以及临床相关复杂MND的患病率。三个生育力低下组的神经状况并无显著差异：每个生育力低下组的NOS中位数均为53，三个生育力低下组中复杂MND的患病率分别为30%、37%和36%。然而，生育力低下夫妇所生孩子的NOS较低，复杂MND的患病率高于生育正常夫妇的孩子（调整后的平均差异[95%可信区间]：-4.48[-5.53至-3.42]），调整后的比值比[95%可信区间]分别为5.13[2.60 - 10.16]。我们得出结论，卵巢刺激、体外操作以及两者的结合与9岁单胎较差的神经结局并无关联。然而，在9年的随访中，父母生育力低下与子代较差的神经结局有关。
