胚胎著床前基因診斷於相互轉位及羅柏森氏轉位之應用

Abstract

研究背景：胚胎之染色體非整倍體是人工試管嬰兒失敗、流產最主要原因。在染色體平衡性轉位(相互轉位及羅伯森氏轉位)之夫婦有很高機會產生不平衡的配子，導致試管嬰兒失敗。胚胎著床前基因診斷(pre-implantation genetic diagnosis, PGD)可以檢測染色體的數目有無增減，同時偵測有無大片段的缺失或轉位，篩選正常胚胎，植入母體，增加試管嬰兒之成功機率。以往的研究應用螢光染色原位雜交技術（fluorescent in situ hybridization，FISH）執行PGD，成功率為28.6%。然而FISH診斷率過低，所以本研究希望應用晶片式比較基因體雜交技術(Array comparative genomic hybridization；Array-CGH)及囊胚期胚胎切片提高平衡性轉位夫婦試管嬰兒療程之成功率。 材料及方法：本研究收集17 例攜帶染色體平衡性轉位夫婦共執行23 個cycle的PGD。從2011年1月至2013年3月，個案至台大醫院人工生殖中心，經遺傳諮詢後接受試管嬰兒療程並執行PGD。PGD之胚胎切片採用囊胚期胚胎及Array-CGH，篩選正常胚胎植入。 實驗結果： 本研究有17 例攜帶染色體平衡性轉位夫婦，其中1例是羅伯森氏 轉位、16 例是相互轉位，婦女平均年齡為33.8 歲。 17 例夫妻共執行23 個cycle 的PGD，有四對夫妻共8個週期無胚胎植入，其他13 對夫妻共完成15個週期的治療流程，平均植入1.8 顆胚胎。有9例懷孕，治療週期懷孕率為39.1%(9/23)，三位孕婦流產，流產率為13.0%(3/23)，植入週期活產率為26.1%(6/23)，5 對夫妻共得到6 位健康的寶寶，包含一對雙胞胎，尚有1 對確認懷孕正持續追蹤。臨床結果顯示染色體轉位之夫婦在執行PGD 後的成功治療率為35.3％(6/17 couples)。 結論：應用囊胚期胚胎切片及晶片式比較基因體雜交技術，篩選正常胚胎植入，確實能提高攜帶平衡性轉位夫婦執行人工試管嬰兒之成功率。

Background: The most common reason for In Vitro Fertilization (IVF) failure and abortion is aneuploidy gametes. Translocation carriers (including reciprocal translocation and Robertsonian translocation) have an increased risk of reproductive failure or affected off-springs. Studies have shown that pre-implantation genetic diagnosis (PGD) can detect abnormal chromosome with absence of the large fragment and translocations in embryos. Previous detection method by fluorescent in situ hybridization (FISH ) only had 28.6% of pregnancy rate .We try to verify that the success rate for IVF can be increased by using array comparative genomic hybridization(array-CGH) and blastocyst biopsy. Material and Methods: The study included 17 patients who underwent 23 cycles of PGD for balance translocation carriers who visited the artificial reproductive center of National Taiwan University Hospital. They performed IVF treatment and PGD from January 2011 to March 2013. PGD used blastocyst biopsy and array-CGH screening. Results: There are 17 couples with balanced translocation. The average female age is 33.8 years old. One couple had Robertsonian translocation, and 16 couples had reciprocal translocation. 17 patients who underwent 23 cycles of PGD but no balance embryo was found in 8 cycles for four couples. The other13 couples completed 15 cycles of PGD and the average transfer embryo was 1.8 pieces. 9 couples got pregnant and pregnancy rate per cycle was 39.1% (9/23). Three women had miscarriage and abortion rate was 13.0 % (3/23). The live birth rate per cycle was 26.1 % (6/23). Five patients delivered 6 healthy babies including a set of twins and one pregnant couple is confirmed. The study showed that the success rate for couples with PGD was 35.3%(6/17couples)。 Conclusion: Application of blastocyst biopsy and array-CGH can enhance the success rate for balance translocation carriers of In Vitro Fertilization.