基于二代测序技术比较父源与母源性染色体相互易位携带者子代染色体差异
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摘要
目的采用二代测序方法比较父源与母源性染色体相互易位携带者子代染色体差异。方法回顾性分析染色体相互易位夫妇行胚胎植入前遗传学诊断(PreimplantationGeneticDiagnosis,PGD)的52个周期,其中女方携带者31个周期(A组),男方携带者21个周期(B组)。比较两组间患者一般特点、促排卵情况、胚胎发育情况及子代胚胎染色体情况。结果两组一般特点及促排卵情况均无明显差异。两组平均活检胚胎个数无差异(3.68±2.02vs3.57±2.64,P=0.87),B组周期平均整倍体胚胎数高于A组,但差异无显著性(1.43±1.29vs0.90±0.79,P=0.11)。比较胚胎染色体形成情况:B组正常/平衡胚胎比例明显高于A组(40.0%vs24.8%,P=0.02),B组总体不平衡胚胎比例(44.0%vs54.0%,P=0.18)及总体非整倍体/拷贝数变异胚胎比例(32.0%vs42.5%,P=0.15)都低于A组,但差异不具有显著性。两组患者均有约30%的周期无正常/平衡胚胎移植(33.3%vs 31.8%,P=0.84)。结论①染色体平衡易位亲本来源不影响PGD每周期平均活检胚胎数;②母源性相互易位携带导致子代正常/平衡胚胎比例显著降低,不平衡及非整倍体/拷贝数变异胚胎比例一定程度升高。③父母源性相互易位PGD均存在约30%无可移植周期。
Objective:To compare the effect of maternal/paternal source of reciprocal translocation on the chromosome formation during meiosis based on next generation sequence technology. Methods:A retrospective analysis of 52 cycles of PGD for couples with reciprocal translocations was performed. The female translocation carriers included 31 cycles(Group A)and male translocation carriers included 21 cycles(Group B). The chromosome formation status during meiosis was compared between the two groups. Results The clinical characteristics,COS parameters and results were not significantly different(P>0.05).The number of analytic blastocyst was not significantly different between the two groups(3.68±2.02 vs 3.57±2.64,P=0.87).The number of normal/balanced blastocyst was higher in Group B compared with Group A,but the difference was not significant(1.43±1.29 vs 0.90±0.79,P=0.11). The ratio of normal/balanced embryo was statistically higher in Group B compared with Group A(40.0% vs 24.8%,P=0.02). The ratios of unbalanced and aneuploid/CNV blastocyst were some lower in Group B compared with Group A,but the difference was not significant(44.0% vs P=54.0%,P=0.18;32.0% vs 42.5%,P=0.15).There was nearly 30% cycles cancelled with no normal/balanced embryos in PGD for reciprocal translocation carriers(33.3% vs31.8%,P=0.84). Conclusion:① The source of reciprocal translocations has no effect on the COS parameters and results;②Reciprocal translocations in female significant effect the ratio of normal/balanced embryo. The negative effects of maternal source on the ratios of unbalanced and aneuploid/CNV blastocyst need more data to confirm. ③ There was nearly 30% cycles cancelled due to no chromosomally normal embryo tranferred in PGD for reciprocal translocation carriers.
Objective:To compare the effect of maternal/paternal source of reciprocal translocation on the chromosome formation during meiosis based on next generation sequence technology. Methods:A retrospective analysis of 52 cycles of PGD for couples with reciprocal translocations was performed. The female translocation carriers included 31 cycles(Group A)and male translocation carriers included 21 cycles(Group B). The chromosome formation status during meiosis was compared between the two groups. Results The clinical characteristics,COS parameters and results were not significantly different(P>0.05).The number of analytic blastocyst was not significantly different between the two groups(3.68±2.02 vs 3.57±2.64,P=0.87).The number of normal/balanced blastocyst was higher in Group B compared with Group A,but the difference was not significant(1.43±1.29 vs 0.90±0.79,P=0.11). The ratio of normal/balanced embryo was statistically higher in Group B compared with Group A(40.0% vs 24.8%,P=0.02). The ratios of unbalanced and aneuploid/CNV blastocyst were some lower in Group B compared with Group A,but the difference was not significant(44.0% vs P=54.0%,P=0.18;32.0% vs 42.5%,P=0.15).There was nearly 30% cycles cancelled with no normal/balanced embryos in PGD for reciprocal translocation carriers(33.3% vs31.8%,P=0.84). Conclusion:① The source of reciprocal translocations has no effect on the COS parameters and results;②Reciprocal translocations in female significant effect the ratio of normal/balanced embryo. The negative effects of maternal source on the ratios of unbalanced and aneuploid/CNV blastocyst need more data to confirm. ③ There was nearly 30% cycles cancelled due to no chromosomally normal embryo tranferred in PGD for reciprocal translocation carriers.
引文
[1]Yin B,Zhu Y,Wu T,Shen S,Zeng Y,Liang D.Clinical outcomes for couples containing a reciprocal chromosome translocation carrier without preimplantation genetic diagnosis[J].Int J Gynaecol Obstet,2017,136(3):304-308.
[2]Liao YP,Wang CJ,Liang M,Hu XM,Wu Q.Analysis of genetic characteristics and reproductive risks of balanced complex chromosome rearrangement carriers in China[J].Yi Chuan,2017,39(5):396-412.
[3]Christodoulou C,Dheedene A,Heindryckx B,van Nieuwerburgh F,Deforce D,De Sutter P,Menten B,Van den Abbeel E.Preimplantation genetic diagnosis for chromosomal rearrangements with the use of array comparative genomic hybridization at the blastocyst stage[J].Fertil Steril,2017,107(1):212-219.e3.
[4]Pundir J,Magdalani L,El-Toukhy T.Outcome of preimplantation genetic diagnosis using FISH analysis for recurrent miscarriage in low-risk reciprocal translocation carriers[J].Eur J Obstet Gynecol Reprod Biol,2016,203:214-9.
[5]Wiland E,Hobel CJ,HillD,et al.Successful pregnancy after preimplantation genetic diagnosis for carrier of t(2;7)(p11.2;q22)with high rates of unbalanced sperm and embryos:a case report[J].Prenat Diagn,2008,28(1):36-41
[6]LledóB,Ortiz JA,Morales R,et al.The paternal effect of chromosome translocation carriers observed from meiotic segregation in embryos[J].Hum Reprod,2010,25(7):1843-8.
[7]Idowu D,Merrion K,et al.Pregnancy outcomes following24-chromosome preimplantation genetic diagnosis in couples with balanced reciprocal or Robertsonian translocations[J].Fertil Steril,2015,103(4):1037-42.
[8]Gardner DK,Sakkas D.Assessment of embryo viability:the ability to select a single embryo for transfer-a review[J].Placenta,2003,24,Suppl B:S5.
[9]Bormann CL.Is universal application of blastocystbiopsy with comprehensive chromosome screening for embryo selection ready for prime time[J].Fertil Steril,2013,100(2):e5-6.
[10]Zhang S,Lei C,et al.Analysis of segregation patterns of quadrivalent structures and the effect on genome stability during meiosis in reciprocal translocation carriers[J].Hum Reprod,2018,33(4):757-767.
[11]Ko DS,Cho JW,Park SY,et al.Clinical outcomes of preimplantation genetic diagnosis(PGD)and analysis of meiotic segregation modes in reciprocal translocation carriers[J].Am J Med Genet A,2010,152A(6):1428-33.
[12]Iwarsson E,Malmgren H,Inzunza J,et al.Highly abnormal cleavage divisions in preimplantation embryos from translocation carriers[J].Prenat Diagn,2000,20(13):1038-47.
[13]Xu J,et al.Comparative study of single-nucleotide polymorphism array and next generation sequencing based strategies on triploid identification in preimplantation genetic diagnosis and screen[J].Oncotarget,2016,7(49):81839-81848.
[14]Fiorentino F,Bono S,Biricik A,et al.Application of nextgeneration sequencing technology for comprehensive aneuploidy screening of blastocysts in clinical preimplantation genetic screening cycles[J].Hum Reprod,2014,29(12):2802-13.
[15]朱洁茹,欧建平,朱伟杰.基因测序在胚胎植入前遗传学诊断应用的研究进展[J].生殖与避孕,2016,8(36):666-671.
[16]郑叶,等.121个染色体平衡易位携带者PGD周期COH的卵巢反应性分析[J].现代妇产科进展,2014,3(23):165-170.
[17]孙晓岩,罗海宁,等.父源性染色体异常胚胎植入前遗传学诊断的最新研究进展[J].生殖与避孕,2012,32(11):765-770.
[2]Liao YP,Wang CJ,Liang M,Hu XM,Wu Q.Analysis of genetic characteristics and reproductive risks of balanced complex chromosome rearrangement carriers in China[J].Yi Chuan,2017,39(5):396-412.
[3]Christodoulou C,Dheedene A,Heindryckx B,van Nieuwerburgh F,Deforce D,De Sutter P,Menten B,Van den Abbeel E.Preimplantation genetic diagnosis for chromosomal rearrangements with the use of array comparative genomic hybridization at the blastocyst stage[J].Fertil Steril,2017,107(1):212-219.e3.
[4]Pundir J,Magdalani L,El-Toukhy T.Outcome of preimplantation genetic diagnosis using FISH analysis for recurrent miscarriage in low-risk reciprocal translocation carriers[J].Eur J Obstet Gynecol Reprod Biol,2016,203:214-9.
[5]Wiland E,Hobel CJ,HillD,et al.Successful pregnancy after preimplantation genetic diagnosis for carrier of t(2;7)(p11.2;q22)with high rates of unbalanced sperm and embryos:a case report[J].Prenat Diagn,2008,28(1):36-41
[6]LledóB,Ortiz JA,Morales R,et al.The paternal effect of chromosome translocation carriers observed from meiotic segregation in embryos[J].Hum Reprod,2010,25(7):1843-8.
[7]Idowu D,Merrion K,et al.Pregnancy outcomes following24-chromosome preimplantation genetic diagnosis in couples with balanced reciprocal or Robertsonian translocations[J].Fertil Steril,2015,103(4):1037-42.
[8]Gardner DK,Sakkas D.Assessment of embryo viability:the ability to select a single embryo for transfer-a review[J].Placenta,2003,24,Suppl B:S5.
[9]Bormann CL.Is universal application of blastocystbiopsy with comprehensive chromosome screening for embryo selection ready for prime time[J].Fertil Steril,2013,100(2):e5-6.
[10]Zhang S,Lei C,et al.Analysis of segregation patterns of quadrivalent structures and the effect on genome stability during meiosis in reciprocal translocation carriers[J].Hum Reprod,2018,33(4):757-767.
[11]Ko DS,Cho JW,Park SY,et al.Clinical outcomes of preimplantation genetic diagnosis(PGD)and analysis of meiotic segregation modes in reciprocal translocation carriers[J].Am J Med Genet A,2010,152A(6):1428-33.
[12]Iwarsson E,Malmgren H,Inzunza J,et al.Highly abnormal cleavage divisions in preimplantation embryos from translocation carriers[J].Prenat Diagn,2000,20(13):1038-47.
[13]Xu J,et al.Comparative study of single-nucleotide polymorphism array and next generation sequencing based strategies on triploid identification in preimplantation genetic diagnosis and screen[J].Oncotarget,2016,7(49):81839-81848.
[14]Fiorentino F,Bono S,Biricik A,et al.Application of nextgeneration sequencing technology for comprehensive aneuploidy screening of blastocysts in clinical preimplantation genetic screening cycles[J].Hum Reprod,2014,29(12):2802-13.
[15]朱洁茹,欧建平,朱伟杰.基因测序在胚胎植入前遗传学诊断应用的研究进展[J].生殖与避孕,2016,8(36):666-671.
[16]郑叶,等.121个染色体平衡易位携带者PGD周期COH的卵巢反应性分析[J].现代妇产科进展,2014,3(23):165-170.
[17]孙晓岩,罗海宁,等.父源性染色体异常胚胎植入前遗传学诊断的最新研究进展[J].生殖与避孕,2012,32(11):765-770.
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