Department of Medical Genetics, Shodair Children's Hospital, PO Box 5539, Helena, MT, 59604-5539, USA.
Montana Department of Public Health and Human Services, Helena, MT, USA.
J Assist Reprod Genet. 2018 Jun;35(6):985-992. doi: 10.1007/s10815-018-1228-z. Epub 2018 Jun 24.
In vitro fertilization (IVF) has been linked to an increased risk for imprinting disorders in offspring. The data so far have predominantly been retrospective, comparing the rate of IVF conceptions in affected patients with controls. We describe a series of fetuses with omphalocele that were tested for Beckwith-Wiedemann syndrome (BWS) and subsequently ascertained as to whether pregnancies were conceived by assisted reproductive technologies (ART).
Fetuses were tested for BWS by Southern blot, PCR based methods, and methylation analysis to identify the imprinting status at primarily the IC2 locus, KCNQ1OT1, as well as IC1, H19/IGF-2. Some fetuses were also tested for uniparental disomy of chromosome 11p.
We tested 301 fetuses with omphalocele for BWS. Forty samples were positive. Sixteen were from IVF pregnancies, for an overall rate of 40%. Such as high proportion of IVF pregnancies in a series of BWS-positive fetuses has not been described previously. Possible factors such as twinning and ascertainment bias are discussed.
We found about a 20-fold overrepresentation of IVF cases in fetuses with BWS/omphalocele when compared with the rate of ART pregnancies in the USA (p < .0001). Our series provides support for an association of IVF and BWS. Patients should be counseled about these risks and made aware of the availability of prenatal diagnosis for detection.
体外受精（IVF）已与后代印迹疾病的风险增加相关联。迄今为止，这些数据主要是回顾性的，将受影响患者的 IVF 受孕率与对照组进行比较。我们描述了一系列患有脐膨出的胎儿，这些胎儿接受了 Beckwith-Wiedemann 综合征（BWS）的检测，随后确定了是否通过辅助生殖技术（ART）受孕。
通过Southern blot、基于 PCR 的方法和甲基化分析对胎儿进行 BWS 检测，以确定主要在 IC2 基因座、KCNQ1OT1 以及 IC1、H19/IGF-2 处的印迹状态。一些胎儿还接受了 11p 单亲二体性的检测。
我们对 301 例患有脐膨出的胎儿进行了 BWS 检测。有 40 个样本呈阳性。其中 16 个来自 IVF 妊娠，总体发生率为 40%。在一系列 BWS 阳性胎儿中，IVF 妊娠的比例如此之高，以前尚未有报道。讨论了可能的因素，如双胞胎和确定偏差。
与美国的 ART 妊娠率相比（p<0.0001），我们发现 BWS/脐膨出胎儿中 IVF 病例的代表率约高 20 倍。我们的系列研究为 IVF 和 BWS 之间的关联提供了支持。应向患者提供有关这些风险的咨询，并告知他们可进行产前诊断以进行检测。
