目的:骨化性纤维发育不良(FOP)是一种罕见的常染色体显性疾病,可导致严重的残疾和发病率,以结缔组织内形成异位硬组织为特征。这种疾病的发病率约为全球每200万人中的一人。对于FOP没有已知的单一有效治疗。我们报告了世界上首例健康婴儿在体外受精(IVF)和植入前基因检测单基因疾病(PGT-M)后出生的病例,使用核映射进行FOP。
方法:一名患有FOP的30岁白种人女性与她的伴侣一起寻求PGT-M的IVF,以实现胚胎不受FOP影响的健康妊娠。
方法:夫妇接受IVF和PGT-M,使用Karyomapping作为测试方法。在策划这个案子时采用了多学科的团队方法,考虑到取卵的额外风险,妊娠和分娩妇女FOP。
结果:取卵细胞用5天的泼尼松龙治疗以降低局部炎症反应的风险,这可能导致随后的异位骨化。随后每两天以减少剂量断奶。患者接受了简单的卵母细胞提取,产生12个成熟卵母细胞。卵胞浆内单精子注射(ICSI)后,培养了十个具有两个前细胞核的受精卵,检索后5-6天,有6人接受了滋养外胚层活检和玻璃化。PGT-M通过Karyomapping显示,六个囊胚中有四个(66.7%)不是母体高危FOP等位基因的携带者。总的来说,该患者进行了三次单独的胚胎移植。在第三次冷冻胚胎移植后怀孕,怀孕37周,剖腹产分娩.婴儿出生时状况良好,不受FOP影响。
结论:使用Karyomapping的IVF/ICSI和PGT-M已成功实施,以鉴定携带高风险FOP等位基因的胚胎,从而导致健康的分娩。
OBJECTIVE: Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant condition that leads to significant disability and morbidity, characterised by the formation of heterotopic hard tissues within connective tissues. The condition has an incidence of approximately one per two million people worldwide. There is no known single effective treatment available for FOP. We report the world\'s first
case of a healthy infant born following in vitro fertilisation (IVF) and preimplantation genetic testing for monogenic disorder (PGT-M) using Karyomapping for FOP.
METHODS: A 30-year-old Caucasian female with FOP presented with her partner seeking IVF with PGT-M to achieve a healthy pregnancy with an embryo unaffected by FOP.
METHODS: The couple underwent IVF and PGT-M using Karyomapping as the testing method. A multi-disciplinary team approach was utilised in planning this
case, considering the additional risks of oocyte retrieval, pregnancy and childbirth in women with FOP.
RESULTS: The oocyte retrieval was covered with a 5-day course of prednisolone to reduce the risk of a localised inflammatory reaction, which could result in subsequent heterotopic ossification. This was subsequently weaned down with reducing doses every two days. The patient underwent uncomplicated oocyte retrieval, yielding 12 mature oocytes. Following intracytoplasmic sperm injection (ICSI), ten zygotes having two pro-nuclei were cultured, and six underwent trophoectoderm biopsy and vitrification 5-6 days after retrieval. PGT-M via Karyomapping revealed four out of six (66.7%) of blastocysts were not carriers of the maternal high-risk FOP allele. In total, the patient had three separate embryo transfers. Pregnancy was achieved following the third frozen embryo transfer, which went to 37 weeks\' gestation, and delivered by Caesarean section. The baby was born in excellent condition and is unaffected by FOP.
CONCLUSIONS: IVF/ICSI and PGT-M using Karyomapping was successfully implemented to identify embryos carrying the high-risk FOP allele resulting in a healthy livebirth.