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.

ICSI 后的受精失败 (FF) 和合子停滞对患者和临床医生都有巨大影响，但这两个问题通常是意想不到的，无法正确诊断。幸运的是，近年来，基因测序已经能够识别 ICSI 失败结果背后的多种遗传变异，但这种方法的使用在生育诊所中仍远未达到常规。在这篇系统综述中，对与 FF、受精异常和/或 ICSI 后合子停滞相关的遗传变异进行了汇编和分析。纳入了四十七项研究。记录并分析了 141 名携带 121 种遗传变异（影响 16 个基因）的患者的数据。总共，PLCZ1中有 27 个变体（50 名男性），WEE2中有 26 个变体（在 24 名女性中）是与卵母细胞激活失败相关的两个因素，可以解释高比例的男性相关和女性相关 FF。在WBP2NL、ACTL9、ACTLA7和DNAH17（男性）以及TUBB8、PATL2、TLE6、PADI6、TRIP13、BGT4、NLRP5、NLRP7、CDC20和ZAR1（女性）中报告了其他已鉴定的变异。如实验和/或计算机模拟所证明，这些变异中的大多数是致病性或潜在致病性（89/121，72.9%）接近。大多数个体携带双等位基因变异（89/141，63.1%），但已鉴定出PLCZ1和TUBB8的杂合性致病变异。针对受影响个体的临床治疗方案，例如化学辅助卵母细胞激活 (AOA) 或卵母细胞内注射PLCZ1 cRNA，仍处于实验阶段。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 和合子停滞，并指导患者咨询和未来的研究前景。