平衡易位攜帶者行胚胎植入前遺傳學(xué)診斷的胚胎染色體異常類型分析及妊娠結(jié)局分析
發(fā)布時間：2018-10-05 15:58
【摘要】：背景:平衡易位是常見的染色體異常。平衡易位攜帶者可在配子形成的過程中產(chǎn)生高比例的非整倍體異常配子,從而導(dǎo)致產(chǎn)生不孕、流產(chǎn)及胎兒異常等不良孕產(chǎn)的發(fā)生。胚胎植入前遺傳學(xué)診斷(Preimplantation genetic diagnosis,PGD)能通過檢測胚胎染色體的整倍性,發(fā)現(xiàn)非整倍體胚胎,從而顯著減少移植胚胎后因染色體異常原因引起的流產(chǎn)、胎兒畸形等的發(fā)生率。早期針對胚胎的染色體異常檢測使用熒光原位雜交技術(shù)(Fluorescencein si/u hybridization,FISH),僅能檢測特定的染色體,隨著技術(shù)的發(fā)展,微陣列比較基因組雜交技術(shù)(Array comparative genome hybridization;array-CGH)等技術(shù)均能檢測24條染色體的整倍性,提高了檢測的水平。使用24條染色體檢測技術(shù)檢測出胚胎的染色體異常情況及患者臨床結(jié)局等數(shù)據(jù)分析是遺傳咨詢中重要的參考資料。目的:本研究旨在回顧性分析染色體平衡易位攜帶至夫婦行基于array-CGH的PGD檢測后胚胎中的來源于親緣易位的異常染色體以及新發(fā)異常的比例和異常分布。方法:收集了 2012-2014年于我院使用array-CGH行PGD的平衡易位攜帶者夫婦胚胎的檢測結(jié)果并進行分析。共計261對夫婦(夫婦一方為染色體平衡易位攜帶者),968枚囊胚。根據(jù)檢測結(jié)果將信號異常胚胎是否發(fā)生在與親緣攜帶的平衡易位相關(guān)進行分類。進一步統(tǒng)計非父母易位染色體異常在1-22號常染色體及性染色體上的分布情況。結(jié)果:在968枚胚胎中,934(97.4%934/981)枚胚胎成功檢測。其中27.8%(262/943)為整倍體胚胎,72.2%(681/943)為異常胚胎。在異常胚胎中,異常僅發(fā)生在在親緣易位的染色體的胚胎為52.6%(358/681),異常僅發(fā)生在非親緣平衡易位的染色體上的胚胎有23.3%(159/681),混合染色體異常的胚胎有24.1%(164/681)。出現(xiàn)異常的染色體見于1-22號常染色體及性染色體,以16,15,22,13,10號染色體異常最常見。胚胎分類在不同平衡易位攜帶者性別分組上分布無統(tǒng)計學(xué)意義,不同女方年齡分組的異常胚胎分布差異有統(tǒng)計學(xué)意義。結(jié)論:24條染色體檢測對于平衡易位攜帶者是一個有效減少不良妊娠結(jié)局的助孕方法。平衡易位患者胚胎染色體異常不僅涉及親屬平衡易位染色體,非平衡易位相關(guān)的新發(fā)染色體異常涵蓋1-22號染色體及性染色體,異常最多見于16號染色體,最少見于12號染色體。背景:平衡易位攜帶者有自然流產(chǎn)、復(fù)發(fā)性流產(chǎn)、后代有胎兒異常等高生育風(fēng)險。PGD技術(shù)的興起有效的減少了流產(chǎn)率、提高了活產(chǎn)率。但是少有研究關(guān)注平衡易位攜帶者PGD助孕前后胎兒胎兒異常的變化。根據(jù)相關(guān)文獻報道,在PGD助孕前,平衡易位攜帶者后代常見的胎兒異常有心臟結(jié)構(gòu)異常、神經(jīng)發(fā)育遲滯、先天愚型等等,但是很少文獻報道經(jīng)過PGD助孕后先天缺陷的變化。目的:隨訪使用PGD助孕前后的平衡易位攜帶者夫婦的妊娠結(jié)局;詳細列舉PGD助孕前后其發(fā)生胎兒胎兒異常的具體類型并分析。方法:2012年-2014年就診于山東大學(xué)附屬生殖醫(yī)院,并根據(jù)染色體核型分析結(jié)果診斷為平衡易位并選擇array-CGH技術(shù)行PGD助孕的215對夫婦,共計249個周期。記錄PGD助孕前平衡易位攜帶者夫婦的妊娠情況及移植檢測未見異常的胚胎后的妊娠結(jié)局。并記錄和分析PGD助孕前后所發(fā)生的胎兒異常。結(jié)果:在PGD助孕前,妊娠結(jié)局中最常見的是早期流產(chǎn)64.1%(223/348),最少見的是中晚期流產(chǎn)1.1%(4/348);胎兒異常(不良孕產(chǎn))占5.7%(20/348)。在PGD助孕后,妊娠結(jié)局中14.6%(18/123)為早期流產(chǎn),73.1%(90/123)為正�；町a(chǎn),2.4%(3/123)有胎兒異常。在PGD助孕后,早期流產(chǎn)率相較于PGD助孕前的早期流產(chǎn)率有統(tǒng)計學(xué)差異(P0.001);正�；町a(chǎn)率有統(tǒng)計學(xué)差異(P0.001);而胎兒異常率無統(tǒng)計學(xué)差異(P=0.156)。PGD助孕前,在胎兒先天發(fā)育異常中:30.4%(7/23)為心臟發(fā)育異常最見,17.4%(4/23)為頸部水囊瘤位列其次,13%(3/23)為腦癱。PGD助孕后,出現(xiàn)三例先天缺陷:分別為先天性心臟結(jié)構(gòu)缺陷,多指及喉喘鳴,各占33.3%。結(jié)論:PGD可有效的降低平衡易位攜帶者的早期流產(chǎn)率,提高活產(chǎn)率。經(jīng)PGD助孕后,胎兒/嬰兒常見胎兒異常降低,但是與助孕前對比無統(tǒng)計學(xué)意義。在PGD助孕后,平衡易位攜帶者后代出現(xiàn)與染色體相關(guān)的胎兒異常減少,提示PGD助孕有益于減少因染色體異常導(dǎo)致的胎兒異常的發(fā)生。
[Abstract]:Background: Balanced translocation is a common chromosomal anomaly. A balanced translocation carrier can produce a high proportion of non-ploidy abnormal gametes during gamete formation, leading to the occurrence of unwanted pregnancies such as infertility, miscarriage, and fetal abnormalities. The pre-implantation genetic diagnosis (PGD) can detect the incidence of abortion, fetal malformation and the like caused by chromosomal abnormalities after embryo transfer by detecting the ploidy of the embryo chromosome. fluorescence in situ hybridization (FISH) is used in the early detection of chromosomal abnormalities in embryos, and only specific chromosomes can be detected. With the development of technology, microarray comparative genomic hybridization (ARray-CGH) techniques can detect the ploidy of 24 chromosomes. the level of detection is improved. The analysis of chromosomal abnormalities and clinical outcomes of embryos using 24 chromosome testing techniques is an important reference in genetic counseling. Objective: The purpose of this study was to retrospectively analyze the chromosome balance translocation and the proportion and abnormal distribution of abnormal chromosomes derived from genetic translocation in embryo derived from the PGD based on array-CGH. Methods: The results were collected from 2012 to 2014 in our hospital using array-CGH line PGD, and the results were analyzed. A total of 261 couples (one of whom were chromosome balanced translocation carriers) and a total of 68 blastocyst. The abnormal embryo of the signal is classified according to the detection result whether or not the abnormal embryo of the signal takes place in relation to the balanced translocation carried by the relatives. The distribution of non-parental translocation chromosome abnormalities on chromosome 1-22 and sex chromosome is further counted. Results: 934 (97.4% 934/ 981) embryos were detected successfully in the embryos. Of these, 27. 8% (262/ 943) were ploploid embryos and 72.2% (681/ 943) were abnormal embryos. In the abnormal embryo, only 26.6% (358/ 681) of the embryos in the chromosome of the genetic translocation occurred, and the abnormality occurred only in 23. 3% (159/ 681) of the embryos on the chromosome of the non-related balanced translocation, and the embryo of the mixed chromosome abnormality was 24. 1% (164/ 681). The abnormal chromosomes were found in the chromosome 1-22 and sex chromosomes, and chromosomes 16, 15, 22, 13 and 10 were most common. There was no statistically significant difference in the distribution of embryos in the sex groups of different balanced translocation carriers, and the difference of abnormal embryo distribution among different age groups was statistically significant. Conclusion: 24 chromosome detection is an effective way to reduce adverse pregnancy outcomes for balanced translocation carriers. The abnormal chromosome abnormality of balanced translocation is not only related to family balance translocation chromosome, but the new chromosome abnormalities related to non-balanced translocation include chromosome 1-22 and sex chromosome, the abnormality is most seen in chromosome 16, and at least chromosome 12. BACKGROUND: Balanced translocation carriers have high fertility risks such as spontaneous abortion, recurrent spontaneous abortion, and fetal abnormalities in offspring. The emergence of PGD technology effectively reduces the rate of miscarriage and increases the live birth rate. However, it is rare to focus on the change of fetal fetal abnormalities after PGD for balanced translocation carriers. According to the relevant literature, there are common fetal abnormalities in the offspring of PGD promoter and balanced translocation carriers, such as cardiac structural abnormality, neurodevelopmental delay, congenital disorder, and so on, but few literature reports the change of congenital defects after PGD assisted pregnancy. Objective: To follow up the pregnant outcome of the balanced translocation carriers after the use of PGD and to give a detailed list of the specific types and analysis of fetal fetal abnormalities after PGD. Methods: From 2012 to 2014, I went to the affiliated reproductive hospital of Shandong University, diagnosed as balanced translocation according to the chromosome karyotype analysis, and selected the 215 couples of the array-CGH technique line PGD assisted pregnancy for a total of 249 cycles. To record the pregnancy outcome of the PGD promoter balanced translocation carrier and the post-embryo pregnancy outcome of the transplantation test. and recording and analyzing fetal abnormalities after the PGD promoter. Results: The most common in the outcome of pregnancy was 64.1% (223/ 348) in early abortion and 1% (4/ 348) in middle and late abortion, and 5. 7% (20/ 348) of fetal abnormality (bad pregnancy). After PGD assisted pregnancy, 14. 6% (18/ 123) of the pregnancy outcomes were early miscarriages, 73.1% (90/ 123) were normal live births and 2.4% (3/ 123) had fetal abnormalities. There was a statistically significant difference in the early abortion rate compared with the early abortion rate (P = 0.001) after PGD assisted pregnancy; the normal live birth rate was statistically different (P = 0. 156); and the fetal abnormality rate was not statistically different (P = 0.156). 17. 4% (4/ 23) ranked second and 13% (3/ 23) were cerebral palsy. Three congenital defects occurred after PGD assisted pregnancy: congenital heart structural defects, cerebral palsy and respiratory wheeze, accounting for 33. 3% respectively. Conclusion: PGD can effectively reduce the early abortion rate of balanced translocation carriers and increase the live birth rate. There was no statistically significant difference in fetal/ infant common fetal abnormalities after PGD assisted pregnancy. After PGD assisted pregnancy, the offspring of balanced translocation carriers showed decreased fetal abnormalities associated with chromosomes, suggesting that PGD assisted pregnancy would be beneficial to reduce fetal abnormalities due to chromosomal abnormalities.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R714.8
本文編號：2253994
[Abstract]:Background: Balanced translocation is a common chromosomal anomaly. A balanced translocation carrier can produce a high proportion of non-ploidy abnormal gametes during gamete formation, leading to the occurrence of unwanted pregnancies such as infertility, miscarriage, and fetal abnormalities. The pre-implantation genetic diagnosis (PGD) can detect the incidence of abortion, fetal malformation and the like caused by chromosomal abnormalities after embryo transfer by detecting the ploidy of the embryo chromosome. fluorescence in situ hybridization (FISH) is used in the early detection of chromosomal abnormalities in embryos, and only specific chromosomes can be detected. With the development of technology, microarray comparative genomic hybridization (ARray-CGH) techniques can detect the ploidy of 24 chromosomes. the level of detection is improved. The analysis of chromosomal abnormalities and clinical outcomes of embryos using 24 chromosome testing techniques is an important reference in genetic counseling. Objective: The purpose of this study was to retrospectively analyze the chromosome balance translocation and the proportion and abnormal distribution of abnormal chromosomes derived from genetic translocation in embryo derived from the PGD based on array-CGH. Methods: The results were collected from 2012 to 2014 in our hospital using array-CGH line PGD, and the results were analyzed. A total of 261 couples (one of whom were chromosome balanced translocation carriers) and a total of 68 blastocyst. The abnormal embryo of the signal is classified according to the detection result whether or not the abnormal embryo of the signal takes place in relation to the balanced translocation carried by the relatives. The distribution of non-parental translocation chromosome abnormalities on chromosome 1-22 and sex chromosome is further counted. Results: 934 (97.4% 934/ 981) embryos were detected successfully in the embryos. Of these, 27. 8% (262/ 943) were ploploid embryos and 72.2% (681/ 943) were abnormal embryos. In the abnormal embryo, only 26.6% (358/ 681) of the embryos in the chromosome of the genetic translocation occurred, and the abnormality occurred only in 23. 3% (159/ 681) of the embryos on the chromosome of the non-related balanced translocation, and the embryo of the mixed chromosome abnormality was 24. 1% (164/ 681). The abnormal chromosomes were found in the chromosome 1-22 and sex chromosomes, and chromosomes 16, 15, 22, 13 and 10 were most common. There was no statistically significant difference in the distribution of embryos in the sex groups of different balanced translocation carriers, and the difference of abnormal embryo distribution among different age groups was statistically significant. Conclusion: 24 chromosome detection is an effective way to reduce adverse pregnancy outcomes for balanced translocation carriers. The abnormal chromosome abnormality of balanced translocation is not only related to family balance translocation chromosome, but the new chromosome abnormalities related to non-balanced translocation include chromosome 1-22 and sex chromosome, the abnormality is most seen in chromosome 16, and at least chromosome 12. BACKGROUND: Balanced translocation carriers have high fertility risks such as spontaneous abortion, recurrent spontaneous abortion, and fetal abnormalities in offspring. The emergence of PGD technology effectively reduces the rate of miscarriage and increases the live birth rate. However, it is rare to focus on the change of fetal fetal abnormalities after PGD for balanced translocation carriers. According to the relevant literature, there are common fetal abnormalities in the offspring of PGD promoter and balanced translocation carriers, such as cardiac structural abnormality, neurodevelopmental delay, congenital disorder, and so on, but few literature reports the change of congenital defects after PGD assisted pregnancy. Objective: To follow up the pregnant outcome of the balanced translocation carriers after the use of PGD and to give a detailed list of the specific types and analysis of fetal fetal abnormalities after PGD. Methods: From 2012 to 2014, I went to the affiliated reproductive hospital of Shandong University, diagnosed as balanced translocation according to the chromosome karyotype analysis, and selected the 215 couples of the array-CGH technique line PGD assisted pregnancy for a total of 249 cycles. To record the pregnancy outcome of the PGD promoter balanced translocation carrier and the post-embryo pregnancy outcome of the transplantation test. and recording and analyzing fetal abnormalities after the PGD promoter. Results: The most common in the outcome of pregnancy was 64.1% (223/ 348) in early abortion and 1% (4/ 348) in middle and late abortion, and 5. 7% (20/ 348) of fetal abnormality (bad pregnancy). After PGD assisted pregnancy, 14. 6% (18/ 123) of the pregnancy outcomes were early miscarriages, 73.1% (90/ 123) were normal live births and 2.4% (3/ 123) had fetal abnormalities. There was a statistically significant difference in the early abortion rate compared with the early abortion rate (P = 0.001) after PGD assisted pregnancy; the normal live birth rate was statistically different (P = 0. 156); and the fetal abnormality rate was not statistically different (P = 0.156). 17. 4% (4/ 23) ranked second and 13% (3/ 23) were cerebral palsy. Three congenital defects occurred after PGD assisted pregnancy: congenital heart structural defects, cerebral palsy and respiratory wheeze, accounting for 33. 3% respectively. Conclusion: PGD can effectively reduce the early abortion rate of balanced translocation carriers and increase the live birth rate. There was no statistically significant difference in fetal/ infant common fetal abnormalities after PGD assisted pregnancy. After PGD assisted pregnancy, the offspring of balanced translocation carriers showed decreased fetal abnormalities associated with chromosomes, suggesting that PGD assisted pregnancy would be beneficial to reduce fetal abnormalities due to chromosomal abnormalities.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R714.8
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