Reproductive Genetics, Juno Genetics-Italy, Rome, Italy.
Unit of Molecular Genetics, Center for Advanced Studies and Technology (CAST), "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy.
Hum Reprod. 2024 Sep 1;39(9):1869-1878. doi: 10.1093/humrep/deae157.
IVF laboratories routinely adopt morphological pronuclear assessment at the zygote stage to identify abnormally fertilized embryos deemed unsuitable for clinical use. In essence, this is a pseudo-genetic test for ploidy motivated by the notion that biparental diploidy is required for normal human life and abnormal ploidy will lead to either failed implantation, miscarriage, or significant pregnancy complications, including molar pregnancy and chorionic carcinoma. Here, we review the literature associated with ploidy assessment of human embryos derived from zygotes displaying a pronuclear configuration other than the canonical two, and the related pregnancy outcome following transfer. We highlight that pronuclear assessment, although associated with aberrant ploidy outcomes, has a low specificity in the prediction of abnormal ploidy status in the developing embryo, while embryos deemed abnormally fertilized can yield healthy pregnancies. Therefore, this universal strategy of pronuclear assessment invariably leads to incorrect classification of over 50% of blastocysts derived from atypically pronucleated zygotes, and the systematic disposal of potentially viable embryos in IVF. To overcome this limitation of current practice, we discuss the new preimplantation genetic testing technologies that enable accurate identification of the ploidy status of preimplantation embryos and suggest a progress from morphology-based checks to molecular fertilization check as the new gold standard. This alternative molecular fertilization checking represents a possible non-incremental and controversy-free improvement to live birth rates in IVF as it adds to the pool of viable embryos available for transfer. This is especially important for the purposes of 'family building' or for poor-prognosis IVF patients where embryo numbers are often limited.
体外受精实验室通常在受精卵阶段采用形态学原核评估来识别异常受精的胚胎，认为这些胚胎不适合临床使用。从本质上讲，这是一种基于双亲二倍体对于正常人类生命是必需的观念的假遗传测试，用于评估胚胎的整倍体性，因为异常的整倍体性会导致着床失败、流产，或导致严重的妊娠并发症，包括葡萄胎和绒毛膜癌。在这里，我们回顾了与显示除经典的两个原核以外的原核构型的受精卵胚胎的整倍体评估相关的文献，以及随后的相关妊娠结局。我们强调，虽然原核评估与异常的整倍体结果相关，但在预测发育中的胚胎异常的整倍体状态时特异性较低，而被认为异常受精的胚胎可以产生健康的妊娠。因此，这种普遍的原核评估策略不可避免地导致超过 50%的来自异常原核受精卵的囊胚被错误分类，并导致在体外受精中系统地丢弃潜在可行的胚胎。为了克服当前实践的这一局限性，我们讨论了新的植入前遗传学检测技术，这些技术能够准确识别植入前胚胎的整倍体状态，并建议从基于形态的检查转向分子受精检查作为新的金标准。这种替代的分子受精检查可能是体外受精中活产率的非递增且无争议的改进，因为它增加了可用于转移的可行胚胎数量。这对于“家庭建设”或对于胚胎数量通常有限的预后不佳的体外受精患者尤其重要。
