- 學位論文
囊胚滋養外胚層細胞染色體鑲嵌和內細胞團塊及臨床預後的關係
Association of mosaic trophectoderm cells , inner cell mass and clinical pregnancy outcomes
摘要
研究目的： 胚胎植入前染色體非整倍體檢測 (preimplantation genetic testing for aneuploid ; PGT-A)目的在避免移植非整倍體胚胎來改善體外受精 (in vitro fertilization ;IVF)結果。最近相關研究發現，與整倍體胚胎相比，鑲嵌型胚胎植入可以健康活產但有較低的懷孕率和活產率及較高的流產率。然而，鑲嵌胚胎中的鑲嵌程度對移植後臨床結果的影響仍然存在爭議。本研究旨在研究胚胎鑲嵌程度度對妊娠預後的影響。 研究方法及資料： 本研究為單一中心回溯性的世代研究。對PGT-A後僅具有鑲嵌胚胎的並進行單一胚胎移植的108名女性病人進行分析。鑲嵌胚胎的標記是使用次世代測序的平台，將第 5/6天囊胚滋養外胚層 (trophectoderm; TE) 切片約五至十個細胞，並進一步檢測其染色體數目。其中定義包含 < 50%異常細胞的TE biopsy被歸類為低度鑲嵌(low-mosaic )，而 ≥50%為高度鑲嵌(high-mosaic)。為進一步確認囊胚滋養外胚層和內細胞團 (inner cell mass; ICM) 之間的染色體組成的一致性，使用41個患者所捐贈剩餘的鑲嵌囊胚進行兩者的分析。分析方法以SPSS for windows 22.0版套裝軟體進行「independent-samples t test分析」、「單變數及多變數分析」及「卡方檢定」。 研究結果： 和低度鑲嵌組比較，高度鑲嵌組活產率 (live birth rate ;LBR) 相當 但流產率 (miscarriage; MR) 顯著較高。（LBR：低度鑲嵌與高度鑲嵌：44.5% vs 36%；p=0.45，MR：低度鑲嵌與高度鑲嵌：5.1% vs 30.7%；p = 0.012）。 來自剩餘鑲嵌囊胚的 TE 和 ICM 的分析表明鑲嵌胚胎的內細胞團塊和滋養外胚層染色體檢測一致性差。 結論與建議： 本研究表明，和低度鑲嵌胚胎移植相比，高度鑲嵌胚胎移植有一定的活產率，但有更高早期流產率。鑲嵌胚胎中的內細胞團塊和滋養外胚層之間有著高度不一致，可能解釋為何高度鑲嵌胚胎移植仍能實現健康的活產。
並列摘要
Background Recently, reports showed that embryos identified as mosaic after preimplantation genetic testing for aneuploid (PGT-A) could result in live birth with lower pregnancy and higher pregnancy loss rates compared with euploid embryos. However, the effects of mosaicism level on reproductive outcomes remain controversial. This study aimed to examine the level of mosaicism on pregnancy outcomes. Material and methods Single mosaic embryo transfer was o ered to 108 women who only had mosaic embryos.Mosaic embryos were labeled by utilizing next generation sequencing (NGS) based PGT-A for day 5/6 trophectoderm (TE) biopsies. TE biopsies containing < 50% abnormal cells were classified as low-level mosaicism and >= 50% as high-level mosaicism. To further confirm the concordance of chromosome constitution between TE and inner cell mass (ICM), 41 remaining embryos designated as mosaic blastocysts donated for research were also analyzed. Results Comparable live birth rate (LBR) but higher miscarriage rate (MR) was found in the high-level group. (LBR: low vs. high: 44.5% vs. 36%; p = 0.45, MR: low vs. high: 5.1% vs. 30.7%; p = 0.012). Analyses of TE and ICM from the remaining mosaic blastocysts show a poor concordance. This preliminary study demonstrated that high-level mosaic embryos could result in comparable LBR but higher MR.