ICSI后受精失败(FF)和合子停止对患者和临床医生都有巨大的影响,但是这两个问题通常都是出乎意料的,无法正确诊断。幸运的是,近年来,基因测序允许识别ICSI失败结果背后的多种遗传变异,但是这种方法在生育诊所的使用还远远不是常规的。在这次系统审查中,与FF相关的遗传变异,对ICSI后异常受精和/或受精卵停止进行汇编和分析。纳入了47项研究。记录并分析了来自141名患者的数据,这些患者携带影响16个基因的121个遗传变异。总的来说,PLCZ1中的27个变体(在50个男性中)和WEE2中的26个变体(在24个女性中)是与卵母细胞激活失败有关的两个因素,可以解释高比例的男性相关和女性相关FF。在WBP2NL中报告了鉴定的其他变体,ACTL9,ACTLA7和DNAH17(男性),和TUBB8,PATL2,TLE6,PADI6,TRIP13,BGT4,NLRP5,NLRP7,CDC20和ZAR1(女性)。这些变异大多数是致病性或潜在致病性的(89/121,72.9%),如实验和/或计算机模拟方法所示。大多数个体携带双等位基因变异(89/141,63.1%),但是已经鉴定出PLCZ1和TUBB8的杂合性致病变异。受影响个体的临床治疗选择,例如化学辅助卵母细胞激活(AOA)或在卵母细胞中注射PLCZ1cRNA,仍然是实验性的。总之,对已知致病变异的基因研究可能有助于诊断复发性FF和合子阻滞,并指导患者咨询和未来的研究前景.
Fertilization failure (FF) and zygotic arrest after ICSI have a huge effect on both patients and clinicians, but both problems are usually unexpected and cannot be properly diagnosed. Fortunately, in recent years, gene sequencing has allowed the identification of multiple genetic variants underlying failed ICSI outcomes, but the use of this approach is still far from routine in the fertility clinic. In this systematic
review, the genetic variants associated with FF, abnormal fertilization and/or zygotic arrest after ICSI are compiled and analyzed. Forty-seven studies were included. Data from 141 patients carrying 121 genetic variants affecting 16 genes were recorded and analyzed. In total, 27 variants in PLCZ1 (in 50 men) and 26 variants in WEE2 (in 24 women) are two of the factors related to oocyte activation failure that could explain a high percentage of male-related and female-related FF. Additional variants identified were reported in WBP2NL, ACTL9, ACTLA7, and DNAH17 (in men), and TUBB8, PATL2, TLE6, PADI6, TRIP13, BGT4, NLRP5, NLRP7, CDC20 and ZAR1 (in women). Most of these variants are pathogenic or potentially pathogenic (89/121, 72.9%), as demonstrated by experimental and/or in silico approaches. Most individuals carried bi-allelic variants (89/141, 63.1%), but pathogenic variants in heterozygosity have been identified for PLCZ1 and TUBB8. Clinical treatment options for affected individuals, such as chemical-assisted oocyte activation (AOA) or PLCZ1 cRNA injection in the oocyte, are still experimental. In conclusion, a genetic study of known pathogenic variants may help in diagnosing recurrent FF and zygotic arrest and guide patient counselling and future research perspectives.