GROW-School for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands.
Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands.
Eur J Hum Genet. 2023 Aug;31(8):918-924. doi: 10.1038/s41431-023-01404-x. Epub 2023 Jun 19.
Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder that affects the skin and the nervous system. The condition is completely penetrant with extreme clinical variability, resulting in unpredictable manifestations in affected offspring, complicating reproductive decision-making. One of the reproductive options to prevent the birth of affected offspring is preimplantation genetic testing (PGT). We performed a retrospective review of the medical files of all couples (n = 140) referred to the Dutch PGT expert center with the indication NF1 between January 1997 and January 2020. Of the couples considering PGT, 43 opted out and 15 were not eligible because of failure to identify the underlying genetic defect or unmet criteria for in vitro fertilization (IVF) treatment. The remaining 82 couples proceeded with PGT. Fertility assessment prior to IVF treatment showed a higher percentage of male infertility in males affected with NF1 compared to the partners of affected females. Cardiac evaluations in women with NF1 showed no contraindications for IVF treatment or pregnancy. For 67 couples, 143 PGT cycles were performed. Complications of IVF treatment were not more prevalent in affected females compared to partners of affected males. The transfer of 174 (out of 295) unaffected embryos led to 42 ongoing pregnancies with a pregnancy rate of 24.1% per embryo transfer. There are no documented cases of misdiagnosis following PGT in this cohort. With these results, we aim to provide an overview of PGT for NF1 with regard to success rate and safety, to optimize reproductive counseling and PGT treatment for NF1 patients.
神经纤维瘤病 1 型（NF1）是一种常染色体显性遗传疾病，影响皮肤和神经系统。该疾病完全外显，临床表现存在极大差异，导致受影响的后代表现出不可预测的症状，从而使生殖决策变得复杂。为了防止生育受影响的后代，可以选择胚胎植入前遗传学检测（PGT）。我们回顾性分析了 1997 年 1 月至 2020 年 1 月期间，所有因 NF1 指征而被转诊至荷兰 PGT 专家中心的夫妇（n=140）的医疗档案。在考虑 PGT 的夫妇中，43 对选择不进行 PGT，15 对因未能确定潜在遗传缺陷或不符合体外受精（IVF）治疗标准而不符合条件。其余 82 对夫妇进行了 PGT。IVF 治疗前的生育评估显示，与 NF1 女性的伴侣相比，NF1 男性的不孕比例更高。NF1 女性的心脏评估显示，她们可以进行 IVF 治疗或怀孕，没有禁忌证。对于 67 对夫妇，进行了 143 次 PGT 周期。与 NF1 男性的伴侣相比，受影响的女性在 IVF 治疗中出现并发症的比例并没有更高。转移了 174 个（295 个中的 174 个）未受影响的胚胎，导致 42 个持续妊娠，胚胎移植的妊娠率为 24.1%。在这个队列中，没有记录到 PGT 后误诊的病例。根据这些结果，我们旨在提供关于 NF1 的 PGT 的成功率和安全性概述，以优化 NF1 患者的生殖咨询和 PGT 治疗。
