Fragouli Elpida, Alfarawati Samer, Spath Katharina, Babariya Dhruti, Tarozzi Nicoletta, Borini Andrea, Wells Dagan
Reprogenetics UK, Institute of Reproductive Sciences, Oxford Business Park North, Oxford, OX4 2HW, UK.
Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, UK.
Hum Genet. 2017 Jul;136(7):805-819. doi: 10.1007/s00439-017-1797-4. Epub 2017 Apr 9.
Preimplantation genetic testing for aneuploidy (PGT-A) is widely used in IVF and aims to improve outcomes by avoiding aneuploid embryo transfers. Chromosomal mosaicism is extremely common in early development and could affect the efficacy of PGT-A by causing incorrect embryo classification. Recent innovations have allowed accurate mosaicism detection in trophectoderm samples taken from blastocysts. However, there is little data concerning the impact of mosaicism on viability, and the optimal clinical pathway for such embryos is unclear. This study provides new information concerning the extent to which mosaic preimplantation embryos are capable of producing pregnancies and births. Archived trophectoderm biopsy specimens from transferred blastocysts were analyzed using next generation sequencing (NGS). Unlike other PGT-A methods, NGS accurately detects mosaicism in embryo biopsies. 44 mosaic blastocysts were identified. Their clinical outcomes were compared to 51 euploid blastocysts, derived from a well-matched, contemporary control group. Mosaic embryos were associated with outcomes that were significantly poorer than those of the control group: implantation 30.1 versus 55.8% (P = 0.038); miscarriage rate 55.6 versus 17.2% (P = 0.036); and ongoing pregnancy 15.4 versus 46.2% (P = 0.003). 61% of the mosaic errors affected whole chromosomes and 39% were segmental aneuploidies. Embryo viability is compromised by the presence of aneuploid cells. However, a minority of affected embryos can produce successful pregnancies. Hence, such embryos should not necessarily be excluded, but given a lower priority for transfer than those that are fully euploid. It is recommended that pregnancies established after mosaic embryo transfers be subjected to prenatal testing, with appropriate patient counselling.
植入前非整倍体基因检测（PGT-A）在体外受精中被广泛应用，旨在通过避免移植非整倍体胚胎来改善治疗结果。染色体嵌合现象在早期发育中极为常见，可能会因导致胚胎分类错误而影响PGT-A的效果。最近的创新技术已能够在从囊胚获取的滋养外胚层样本中准确检测嵌合现象。然而，关于嵌合现象对胚胎存活能力的影响的数据很少，且此类胚胎的最佳临床处理途径尚不清楚。本研究提供了有关嵌合植入前胚胎产生妊娠和分娩能力的新信息。使用下一代测序（NGS）技术对已移植囊胚的存档滋养外胚层活检标本进行分析。与其他PGT-A方法不同，NGS能够准确检测胚胎活检中的嵌合现象。共鉴定出44个嵌合囊胚。将它们的临床结局与来自匹配良好的当代对照组的51个整倍体囊胚进行比较。嵌合胚胎的结局明显比对照组差：着床率分别为30.1%和55.8%（P = 0.038）；流产率分别为55.6%和17.2%（P = 0.036）；持续妊娠率分别为15.4%和46.2%（P = 0.003）。61%的嵌合错误影响整条染色体，39%为节段性非整倍体。非整倍体细胞的存在会损害胚胎的存活能力。然而，少数受影响的胚胎仍可成功妊娠。因此，此类胚胎不一定应被排除，但与完全整倍体的胚胎相比，其移植优先级应较低。建议对嵌合胚胎移植后建立的妊娠进行产前检测，并给予患者适当的咨询。
