生殖医学杂志

目的通过回顾性分析选择胚胎植入前遗传学检测(PGT)助孕的不同特征人群的胚胎遗传检测结果及妊娠结局,探讨影响其妊娠结局的相关因素从而明确可能的临床预测指标。方法回顾性分析2011年6月至2019年12月于南京医科大学第一附属医院生殖医学中心行PGT助孕的1 602个取卵周期及其相应复苏移植周期。第一部分根据夫妇双方染色体是否正常分类,其中夫妇染色体均正常的分为有复发性流产病史的PGT-A组(n=308)及没有流产史但有遗传病生育风险的PGT-M组(n=108);夫妇双方至少一方染色体核型异常者,根据染色体核型分为普通易位组(n=829)和罗氏易位组(n=357),并将两组根据易位发生的性别差异分为普通易位发生在女方(A组,n=387)、男方(B组,n=442),罗氏易位发生在女方(C组,n=145)、男方(D组,n=212)。第二部分以男方精子DNA碎片指数(DNA fragmentation index,DFI)20%为临界值,将1 066个周期分为低DFI组(n=890)和高DFI组(n=176)。比较各组临床指标、实验室指标、胚胎检测结果及妊娠结局。结果 (1)PGT-A组与PGT-M组相比较,染色体异常率(2.17%vs. 1.26%)、胚胎异常率(49.23%vs. 38.17%)较高(P<0.01),D3胚胎形成率(89.92%vs. 93.37%)、囊胚形成率(59.79%vs. 64.81%)、累积妊娠率(74.62%vs. 91.86%)较低(P<0.05);流产率(16.75%vs. 7.59%)较高(P<0.05),累积活产率(69.04%vs. 73.42%)和患者基础情况差异无统计学意义(P>0.05)。(2)与罗氏易位组相比较,普通易位组染色体异常率(3.86%vs. 2.08%)、胚胎异常率(73.53%vs. 57.74%)较高(P<0.01),囊胚形成率(54.38%vs. 58.74%)、累积妊娠率(81.50%vs. 87.23%)较低(P<0.05),两组流产率(6.86%vs. 9.62%)、累积活产率(80.61%vs. 81.17%)和患者基础情况差异无统计学意义(P>0.05)。A组与B组相比较,卵裂率显著下降(98.49%vs. 99.04%)(P<0.05);C组与D组相比较,D3胚胎形成率显著下降(88.51%vs. 91.28%)(P<0.01)。(3)低DFI组与高DFI组相比较,染色体异常率(2.88%vs. 3.40%)和胚胎异常率(60.64%vs. 65.44%)显著下降(P<0.05),MⅡ受精率显著升高(86.47%vs. 84.37%)(P<0.05)。精子DFI与男方年龄有正相关关系(r=0.133,P<0.01);控制双方年龄变量,DFI与染色体异常率仍呈正相关(r=0.105,P<0.01),而与胚胎异常率不相关(r=0.057,P>0.05)。结论 PGT-A组夫妇胚胎染色体异常率更高,PGT-A可在一定程度上改善其妊娠结局;普通染色体易位夫妇较罗氏易位夫妇更难获得正常胚胎,但选择PGT助孕可改善其妊娠结局;精子DFI增加导致胚胎的染色体异常率升高,但对选择PGT助孕患者临床妊娠结局的影响还需更大样本量的研究。

Objective:To analyze the of embryo genetic testing results and pregnancy outcomes in different characteristics patients choosing pre-implantation genetic testing(PGT),in order to explore the relevant factors affecting pregnancy outcomes and identify its possible clinical predictors.Methods:A retrospective analysis was made on 1 602 oocyte retrieval cycles and subsequent implantation cycles undergone PGT in the Clinical Center of Reproductive Medicine,the First Affiliated Hospital of Nanjing Medical University from June 2011 to December 2019. The cycles firstly were classified according to whether the chromosomes of the couple were normal. Both couples with normal chromosomes were divided into PGT-A(PGT for aneuploidy)group(n=308)with a history of recurrent abortion and PGT-M(PGT for monogenetic disease)group(n=108)without an abortion history but with reproductive risk of genetic diseases. The couples at least one partner had chromosomal karyotype abnormalities were divided into general translocation group(n=829)and Robertsonian translocation group(n=357). According to the gender difference in translocation,the two groups were subdivided into ordinary translocations in women(group A,n=387)& man(group B,n=442),and Robrtsonian translocations in women(group C,n=145)& the man(group D,n=212). Secondly,a cut-off value for sperm DNA fragmentation index(DFI)of 20% was used to allocate 1 066 oocyte extraction cycles into low DFI group(n=890)and high DFI group(n=176). The clinical indicators,laboratory indicators,embryo testing results and pregnancy outcomes of each group were compared among the groups.Results:The chromosome abnormality rate(2.17% vs. 1.26%),embryo abnormality rate(49.23% vs. 38.17%)and abortion rate(16.75% vs. 7.59%)were significantly higher(P<0.05),but Day 3 embryo formation rate(89.92% vs. 93.37%),blastocyst formation rate(59.79% vs. 64.81%)and cumulative pregnancy rate(74.62% vs. 91.86%)were significantly lower in PGT-A group compared with PGT-M group(P<0.05)There was no significant difference in the cumulative live birth rate and basic status between the two groups(P>0.05). Compared with the Robrtsonian translocation group,the chromosomal abnormality rate(3.86% vs. 2.08%)and embryo abnormality rate(73.53% vs. 57.74%)(P<0.01)were significantly higher,but the blastocyst formation rate(54.38% vs. 58.74%)and cumulative pregnancy rate(81.50% vs. 87.23%)were significantly lower in the ordinary translocation group(P<0.05). There was no significant difference in abortion rate(6.86% vs. 9.62%),cumulative live birth rate(80.61% vs. 81.17%)and basic status between the two groups(P>0.05). The cleavage rate(98.49% vs. 99.04%)in group A was significantly lower than that in group B(P<0.05). The Day 3 embryo formation rate in group D was significantly lower than that in group C(88.51% vs. 91.28%)(P<0.01). The chromosomal abnormality rate(2.88% vs. 3.40%)and embryo abnormality rate(60.64% vs. 65.44%)were significantly lower(P<0.05),but the MⅡ fertilization rate was significantly higher(86.47%vs. 84.37%,P<0.05)in the low DFI group compared with high DFI group. There is a positive correlation between sperm DFI and male age(r=0.133,P<0.01). After controlling for both age variables,DFI was still positively correlated with chromosomal abnormality rate(r=0.105,P<0.01),but not correlated with embryo abnormality rate(r=0.057,P>0.05).Conclusions:The chromosomal abnormality rate of PGT-A group is higher. Usage of PGT-A can improve the pregnancy outcome to some extent. Normal embryos are more difficult to obtain for couples with ordinary chromosomal translocations than for those with Robrtsonian translocations,but the use of PGT can improve pregnancy outcomes of the former. Increased sperm DFI leads to an increase of chromosomal abnormalities rate in embryos,but the effect on clinical pregnancy outcomes needs to be studied with a larger sample size.