平衡易位携带者孕中期产前诊断结果分析

目的:探讨平衡易位携带者孕中期胎儿产前诊断结果及妊娠结局,为平衡易位携带者遗传咨询及生育指导提供科学依据。方法:选择2015年1月至2016年12月夫妻之一为平衡易位携带者65例,于妊娠18~24周在我院行羊水染色体核型检查,并针对检测结果进行分析。结果:65例平衡易位携带者,28例(43.1%)胎儿染色体核型正常,25例(38.5%)胎儿为平衡易位携带者,12例(18.4%)胎儿为不平衡易位患者。其中总妊娠次数为187次,早期流产总次数为122次(65.2%);妊娠活产53次(28.3%),此次妊娠活产率81.5%(53/65);引产12次(6.4%)。13号与14号染色体发生相互易位的几率最高(16.2%,19.2%),其生育不平衡胎儿的几率分别为4.8%和12.0%。结论:平衡易位携带者夫妇其早期流产发生率较高,妊娠到孕中期后获得染色体正常后代和平衡易位携带者后代的几率较高,选择自然妊娠并进行产前诊断来获取健康后代是完全可行的。不同染色体发生易位其生育不平衡后代几率不同。     

染色体易位的植入前遗传学诊断

目的 观察染色体平衡易位和罗伯逊(罗氏)易位基因携带者夫妇进行植入前遗传学诊断(PGD)后的胚胎染色体遗传特征和胚胎着床、妊娠情况,探讨PGD在染色体易位基因携带者夫妇实现正常生育中的意义.方法 用荧光原位杂交(FISH)技术对36对夫妇的胚胎进行PGD,其中14例为染色体平衡易位(平衡易位组),22例为染色体罗氏易位(罗氏易位组),并对诊断结果和胚胎着床、妊娠情况进行分析.结果 36例患者共活检胚胎253个,成功诊断胚胎225个,成功率为88.9%(225/253),获得可供移植的正常或平衡的胚胎共58个.平衡易位组和罗氏易位组PGD后胚胎着床率分别为36%(5/14)和14%(6/44),临床妊娠率分别为4/9和26%(5/19).结论 PGD可有效诊断胚胎染色体平衡易位和罗氏易位,避免反复流产和不必要的非意愿性终止妊娠,并获得理想的胚胎着床率和临床妊娠率.     

121个染色体平衡易位携带者PGD周期COH的卵巢反应性分析

目的:探讨常染色体平衡易位对女性携带者控制性超促排卵(COH)中卵巢反应性的影响。方法:回顾分析于我院行胚胎植入前遗传学诊断(PGD)的109对常染色体平衡易位夫妇,共121个周期,其中夫妇中仅女方为平衡易位携带者56例(63个周期,研究组),包括罗伯逊易位携带者23例(27个周期),相互易位携带者33例(36个周期);夫妇中仅男方为平衡易位携带者53例(58个周期,对照组),包括罗伯逊易位携带者30例(32个周期),相互易位携带者23例(26个周期)。分析COH过程中,研究组和对照组的女方卵巢反应性指标和妊娠结局。结果:两组的女方年龄、体重指数(BMI)、基础内分泌及窦卵泡数(AFC)均无显著差异(P0.05)。两组的卵巢反应性指标,包括Gn总量、HCG注射日E2水平、获卵数、D3胚胎数、可移植胚胎数及移植胚胎数,以及移植周期临床妊娠率、早期流产率及种植率均无显著差异(P0.05)。单独就罗伯逊易位携带者或相互易位携带者而言,两组的各指标均无显著差异。排除可能影响COH卵巢反应性的女方因素,研究组与对照组的各指标均无显著差异。结论:染色体平衡易位,包括罗伯逊易位或相互易位并不影响COH中的卵巢反应性。应将染色体平衡易位女性携带者视为正常卵巢反应性,采用合适剂量的促性腺激素进行控制性促排卵。     

22例染色体平衡易位携带者优生遗传咨询

本文对我科自1982年8月至1991年12月间检出的22例平衡易位携带者进行分析,结果显示:此组病人以反复自然流产而就诊者最多,占77.27％;其次是曾分娩畸形儿死胎者,占9.09％。染色体核型分析以罗伯逊易位为最多,占81.82％,其中非同源染色体罗伯逊易位占77.78％,同源染色体罗伯逊易位占22.22％;染色体相互易位占18.18％。本文建议同源染色体罗伯逊易位者,应劝其绝育,非同源染色体平衡易位者,可于孕中期取羊水细胞培养进行产前诊断。     

产前诊断中染色体非平衡易位胎儿33例临床分析

目的探讨产前诊断中非平衡相互易位胎儿的产前诊断指征、临床特征及妊娠结局,为孕妇妊娠选择提供遗传学依据。方法对2011年5月至2016年2月行羊水染色体核型分析并诊断为非平衡相互易位的33例患者的临床资料进行回顾性分析。结果 33例非平衡易位患者中,28例(84.8%,28/33)胎儿超声异常,5例(15.1%,5/33)胎儿超声结果未见异常。7例(21.2%,7/33)为新发突变易位,26例(78.8%,26/33)为父母系遗传易位。7例新发突变的主要产前诊断指征为超声异常5例,高龄2例。26例遗传易位中,双亲之一为易位携带者10例,超声异常8例,高龄5例及不良生育史3例,其中10例(38.5%,10/26)产前检查前双亲之一就已知为易位携带者,16例(61.5%,16/26)为产前检查后确诊。33例均选择终止妊娠,其中28例与超声异常特征相符,5例未见明显表型异常特征。结论产前诊断指征中超声异常与非平衡相互易位紧密相关,异常的染色体易位核型大部分来源于双亲之一平衡易位携带者。非平衡易位胎儿由于涉及染色体大片段的丢失或重复,易导致显著的畸形表型特征,通常均需终止妊娠。     

76例羊水胎儿染色体结构异常临床分析

目的通过对妊娠中期孕妇羊水染色体结构异常产前诊断指征分布、发病率及妊娠结局的分析,探讨妊娠中期胎儿染色体结构异常的妊娠结局。方法对2011年2月至2015年3月2 562例羊水染色体检查中76例染色体结构异常孕妇的临床资料进行回顾性分析。结果 2 562例羊水标本中,检出76例(2.97%)染色体结构异常,其中染色体倒位29例,相互易位25例,不平衡易位11例,复杂重排5例,其他结构异常6例。76例患者中,55例患者选择继续妊娠,其中29例染色体倒位,23例相互易位,3例复杂重排;21例患者选择终止妊娠,其中染色体不平衡易位11例,复杂重排2例,其他结构异常6例,X与常染色体新发突变易位1例,遗传型易位伴Turner综合征1例。结论产前诊断中羊水染色体结构异常主要为染色体倒位、相互易位、不平衡易位及复杂重排。绝大部分相互易位及倒位的结构异常可以选择继续妊娠。不平衡易位及复杂重排由于涉及基因片段的增加或丢失,大部份选择终止妊娠。     

勘误

<正>本刊2014年第23卷第3期刊登的文章《121个染色体平衡易位携带者PGD周期COH的卵巢反应性分析》(P165-170)中1.1研究对象中"研究组纳入37例(41个周期,包括罗伯逊易位携带者17个周期和相互易位携带者22个周期),对照组为37例(41个周期,包括罗伯逊易位携带者24个周期和相互易位携带者19个周期)"应为"研究组纳入37例(41个周期,包括罗     

妊娠中期羊水染色体检查662例临床分析

目的 分析妊娠中期染色体病高危胎儿染色体病的发生状况.方法 对2003年9月至2007年3月间中国医科大学附属盛京医院662例染色体病高危孕妇进行羊膜腔穿刺,采取羊水细胞培养,制备中期染色体,分析胎儿核型,进行产前诊断.结果 发现染色体异常21例,异常率3.2%,其中数目异常11例,结构异常10例,不同产前诊断指征分组中的异常率不同,以夫妇双方之一为平衡易位携带者组异常率最高,为53.8%.结论 妊娠中期对染色体病高危孕妇进行羊水细胞培养染色体核型分析是产前诊断的重要手段,孕母血清筛查阳性、高龄、超声检查异常及染色体平衡易位携带者是羊水染色体检查的指征.     

具有高遗传风险的孕妇其孕早期染色体、DNA、代谢的研究结果

本文描述了1,034例具有染色体病和代谢病风险孕妇的绒毛研究结果及随访资料。(1)在574例高龄孕妇中,检测出16例胎儿异常核型(7例21三体,6例18三体,3例性染色体异常)和2例家族性倒位携带者,所有异常胎儿的孕妇,均终止妊娠,并经流产胎儿细胞核型分析得到进一步确诊。(2)在200例具有复发风险(153例为三体,其中126例为21三体)的孕妇中,检测出2例家族性倒位和易位的携带者,4例染色体结构异常(2例21三体,1例XXY,1例为Fanconi贫血),染色体断裂均明显增加。(3)研究了50例产前诊断胎儿为易位携带者的孕妇。20例为罗伯逊易位,其中7例正常,13例平衡易位;30例相互易位,其中12     

染色体相互易拉携带者的性别和易位片段长度对生育的影响

目的 探讨染色体相互易位携带者的性别和易位片段长度与生育的关系,为遗传咨询提供参考。方法 收集相互易位核型７１４例,综合分析涉及染色体不同部位的染色体异常和易位携带者性别对妊娠结局的影响。结果 相互易位携带者妊娠结局以孕早期流产为主;随着易位片段增长,孕早期流产的比例增加,而生育染色体异常后代的风险减小;女性易位携带者较男性易位携带者易生育染色体异常后代,而男性易位携带者易出现不同程度不育。结论：     

Recurrent pregnancy losses and parental chromosome abnormalities: a review

Summary. A compilation of the cytogenetic results taken from 79 published surveys of couples with two or more pregnancy losses (comprising 8208 women and 7834 men) showed an overall prevalence of major chromosome abnormalities of 2.9%. This is five to six times higher than that of the general adult population. In every group of chromosome abnormalities in the parents a predominance of female to male affected was noted (2:1). Approximately 50% of all chromosome abnormalities detected were balanced reciprocal translocations, 24% were Robertsonian translocations, 12% were sex chromosomal mosaicisms in females, and the rest consisted of inversions and other sporadic abnormalities. Parents with two or more idiopathic pregnancy losses should be karyotyped to aid in management and counselling. When a translocation or other abnormality (e.g. X chromosomal mosaicism) predisposing to an abnormal zygote is found, prenatal diagnosis is indicated in future pregnancies. Even when parental karyotypes are normal, prenatal diagnosis should be considered in subsequent pregnancies of parents with two or more pregnancy losses because of the high incidence of chromosome abnormalities in spontaneous abortions. For the same reason, if a single previous pregnancy loss is known to have been chromosomally aneuploid, parental karyotypes may have to be examined (depending upon the finding in the pregnancy loss), and prenatal diagnosis should also be considered in subsequent pregnancies.     

Cytogenetic studies in couples with repeated spontaneous abortions

Chromosome studies were carried out on both partners of 509 couples with a history of two or more spontaneous abortions. 1) Twenty-six individuals (2.6%) were carriers of a major chromosome abnormality. This incidence is at least six to seven times higher than that in the general adult population. 2) Of these, 10 were reciprocal translocations, 10 robertsonian translocations and 6 numerical aberrations of gonosomes. None of the carriers showed abnormal phenotypes. 3) Chromosome aberrations were more frequent in the women than in their husbands. There were 19 abnormalities in females and 7 in males. 4) The use of banding techniques in chromosome analysis improves the detection of balanced reciprocal translocations. 5) Prenatal diagnosis was performed in 5 subsequent pregnancies of 4 balanced translocation carriers. The fetal karyotypes were 2 normal and 3 balanced translocations. It would seem reasonable to recommend chromosome analysis for couples with repeated spontaneous abortions.     

Chromosome abnormalities in 118 couples with recurrent spontaneous abortions

Cytogenetic studies were carried out on 118 couples with recurrent spontaneous abortions. Four major chromosomal abnormalities were found including two 13/14 Robertsonian translocations, one t(7;12) and one t(1;10) reciprocal translocation. The incidence of chromosomal abnormalities in this study was 3.39%, which is lower than the mean value of the published data. The clinical significance of balanced translocations in recurrent reproductive loss is discussed.     

Recurrent pregnancy losses and parental chromosome abnormalities: a review

A compilation of the cytogenetic results taken from 79 published surveys of couples with two or more pregnancy losses (comprising 8208 women and 7834 men) showed an overall prevalence of major chromosome abnormalities of 2.9%. This is five to six times higher than that of the general adult population. In every group of chromosome abnormalities in the parents a predominance of female to male affected was noted (2:1). Approximately 50% of all chromosome abnormalities detected were balanced reciprocal translocations, 24% were Robertsonian translocations, 12% were sex chromosomal mosaicisms in females, and the rest consisted of inversions and other sporadic abnormalities. Parents with two or more idiopathic pregnancy losses should be karyotyped to aid in management and counselling. When a translocation or other abnormality (e.g. X chromosomal mosaicism) predisposing to an abnormal zygote is found, prenatal diagnosis is indicated in future pregnancies. Even when parental karyotypes are normal, prenatal diagnosis should be considered in subsequent pregnancies of parents with two or more pregnancy losses because of the high incidence of chromosome abnormalities in spontaneous abortions. For the same reason, if a single previous pregnancy loss is known to have been chromosomally aneuploid, parental karyotypes may have to be examined (depending upon the finding in the pregnancy loss), and prenatal diagnosis should also be considered in subsequent pregnancies.     

Data on Families of Chromosome Translocation Carriers Ascertained Because of Habitual Spontaneous Abortion

Cytogenetic studies were performed on 1,180 individuals--490 couples + 200 females presenting with habitual spontaneous abortion (HSA). These revealed 24 abnormal results (2.03%)--15 were apparently balanced reciprocal translocations and 9 were Robertsonian translocations. Of 97 pregnancies among the translocation carriers, there were 10 living children and 87 pregnancy losses--a loss rate of 89.7%. There were 11 familial translocations. In 10 familial cases with a full family tree, there were 27 spontaneous abortions and 64 livebirths among the 30 adult translocation carrier relatives--a loss rate of 29.6%. This is twice the risk found in the general population but not as high as in the probands, who had 6 times the abortion rate in the general population. Mechanisms are suggested for this difference. The subsequent pregnancy history of 12 index translocation couples showed an apparently improved pregnancy outcome with 13 further fetal losses and 13 living children, over a follow-up time per patient ranging from 1-5.5 years. However, when the pregnancy losses at ascertainment were combined with postascertainment losses, the overall rate of pregnancy loss remained the same.     

Natural selection between day 3 and day 5/6 PGD embryos in couples with reciprocal or Robertsonian translocations

Purpose

For translocation carriers, preimplantation genetic diagnosis (PGD) provides the opportunity to distinguish between normal/balanced and unbalanced embryos prior to implantation and, as such, increases the likelihood of a successful ongoing pregnancy. The data presented here compares autosomal reciprocal and Robertsonian translocation segregation patterns in day 3 versus day 5/6 IVF-PGD embryos to determine if there is a difference in the chromosome segregation patterns observed at these developmental time points.

Methods

A retrospective analysis on PGD translocation carriers at Monash IVF was performed. Segregation patterns were compared between day 3 and day 5/6 embryos to ascertain whether selection against malsegregants exists.

Results

For reciprocal translocations, 1649 day 3 embryos (139 translocations) from 144 couples and 128 day 5/6 embryos (59 translocations) from 60 couples were analysed. Day 3 segregation analysis showed that 22.3% of embryos were normal/balanced (consistent with 2:2 alternate segregation) and 77.7% were unbalanced (malsegregation). Day 5/6 segregation analysis showed that 53.1% of embryos were normal/balanced and 46.9% were unbalanced. For Robertsonian translocations, 847 day 3 embryos (8 translocations) from 54 couples and 193 day 5/6 embryos (6 translocations) from 31 couples were analysed. Day 3 segregation analysis showed that 38.7% of embryos were normal/balanced (consistent with 2:1 alternate segregation) and 61.3% were unbalanced. Day 5/6 segregation analysis showed that 74.1% of embryos were normal/balanced and 25.9% were unbalanced.

Conclusions

This data demonstrates an increase in the proportion of genetically normal/balanced embryos at day 5/6 of development. This suggests a strong natural selection process between day 3 and day 5/6 in favour of normal/balanced embryos. These findings support performing PGD testing on day 5/6 of embryo development.

     

Prenatally diagnosed balanced chromosome rearrangements: eight years' experience

OBJECTIVE: To investigate the incidence and pregnancy outcome of prenatally diagnosed balanced chromosome rearrangements from amniocentesis. STUDY DESIGN: Between January 1996 and December 2003, we collected cases with balanced chromosome rearrangements from amniocentesis specimens submitted to our cytogenetics laboratory for fetal karyotyping. Data on maternal age, indication for amniocentesis, detailed anatomic sonographic findings, gestational age at delivery, newborn birth weight and infant anomalies, if any, were obtained by chart review. RESULTS: A total of 66 cases of balanced chromosomal translocations or inversions were identified from the 12,468 amniocentesis specimens. Specifically, 0.256% had a reciprocal translocation, 0.080% had a Robertsonian translocation, and 0.192% had an inversion. The incidences of de novo reciprocal translocations, Robertsonian translocations and inversions were 0.080%, 0.016% and 0.024%, respectively. Abnormal prenatal sonographic findings occurred in 2 cases, 1 in an inherited case and 1 in a de novo case. Abnormal postnatal findings occurred in 5 cases, 3 in inherited cases and 2 in de novo cases. Excluding the cases with minor congenital anomalies, the major congenital anomaly rates of inherited and de novo chromosome rearrangements were 1.96% and 6.66%, respectively. CONCLUSION: The incidences of prenatally diagnosed de novo reciprocal translocations, de novo Robertsonian translocations and de novo inversions were higher than those reported in previous, larger series. The major congenital anomaly rates for inherited and de novo chromosome rearrangements were higher than the 1.4% congenital anomaly rate in our general population. Consequently, detailed ultrasound examination and parental karyotyping should be viewed as essential measures in dealing with prenatally diagnosed balanced chromosome rearrangements.     

Cytogenetic study of peripheral lymphocyte culture in couples with habitual abortion

We report on a cytogenetic investigation of lymphocytes in 241 couples and six women with at least three abortions. We found a balanced reciprocal translocation three times (1.2% of couples) and a balanced Robertsonian translocation twice (0.8% of couples). Four numerical aberrations of the gonosomes were detected (three of them as a mosaic), and one deletion Xq- as a mosaic. The heterochromatic region of the chromosomes 1, 9 or 16 was enlarged in 12 couples (4.9%). There was no couple with a pericentric inversion of the chromosomes 1 or 9. The enlarged Y-chromosome (five males) according to our results does not play any important role for the reproduction. Five translocations and one supernumerary chromosome each in one cell only indicate an enlarged frequency of breakage events in couples with habitual abortion.     

Cytogenetic study in 50 couples with recurrent abortions

The presence of chromosome abnormalities in couples with repeated spontaneous abortion is known even if the phenomenon is far from a complete assessment. A cytogenetic investigation in 50 couples with a history of two or more spontaneous abortions is referred to in this study. A peripheral blood lymphocyte culture was harvested for each subject and the slides were stained by G- and C-banding. Of the 100 individuals examined, 4 were carriers of balanced translocations, 3 of which were of the Robertsonian type. A chromosomal fragility (chromatidic and/or chromosomic gaps) was seen in 2 cases. The incidence of balanced translocations found here is 8% which is near to the mode (about 9%) observed in previous studies. Those frequencies are greater than in the general population (0.1-0.4%). This indicates that balanced translocations have some importance in causing abortion while this is not the case for other chromosomal abnormalities (e.g. pericentric inversions). Thus, cytogenetic analyses should be recommended in couples with repeated spontaneous abortions, when clinical data fail to clarify the cause.