目的:尽管辅助生殖技术(ART)结局已经取得了显着改善,一个关键问题仍然存在:哪个胚胎最有可能导致怀孕?胚胎选择目前基于形态学和遗传标准;然而,这些标准并不能完全预测优质胚胎,因此需要额外的客观标准.卵丘细胞对卵母细胞和胚胎发育至关重要。本系统综述评估了卵丘-卵母细胞复合物中的生物标志物及其与成功IVF结局的关联。
方法:使用PubMed进行了全面搜索,Embase,Scopus,和WebofScience从成立到2022年11月。只包括英文出版物。纳入标准包括评估与人类卵丘细胞(CC)相关的遗传生物标志物和以下三个感兴趣的结果的论文:卵母细胞质量,胚胎质量,和临床结果,包括受精,植入,怀孕,和活产率。
结果:搜索显示446项研究,其中42项符合资格标准。19项研究将CC中的遗传和生化生物标志物与卵母细胞质量相关联。据报道,卵母细胞质量与编码钙稳态(CAMK1D)基因的CC中mRNA表达增加之间存在正相关。葡萄糖代谢(PFKP),细胞外基质(HAS2,VCAN),TGF-β家族(GDF9,BMP15),和前列腺素合成(PTGS2)。19项研究将CC中的遗传和生化生物标志物与胚胎质量相关联。据报道,在编码细胞外基质(HAS2)的基因的CC中,胚胎质量与mRNA表达增加之间存在正相关。前列腺素合成(PTGS2),类固醇生成(GREM1),激素受体编码基因(AMHR2)的表达降低。22项研究评估了CC的遗传和生化生物标志物与临床结果。编码细胞外基质(VCAN)的基因表达增加,TGF-β家族(GDF9、BMP15)与妊娠率呈正相关。
结论:卵丘细胞的遗传生物标志物与卵母细胞质量相关(CAMK1D,PFKP,HAS2,VCAN,GDF-9,BMP-15,PTGS2),胚胎质量(GREM1,PTGS2,HAS2),和妊娠率(GDF9,BMP15,VCAN)。这些结果可能有助于指导针对卵丘细胞测试的未来研究,以设计客观标准来预测IVF结果。
OBJECTIVE: Although significant improvements in assisted reproductive technology (ART) outcomes have been accomplished, a critical question remains: which embryo is most likely to result in a pregnancy? Embryo selection is currently based on morphological and genetic criteria; however, these criteria do not fully predict good-quality embryos and additional objective criteria are needed. The cumulus cells are critical for oocyte and embryo development. This systematic review assessed biomarkers in cumulus-oocyte complexes and their association with successful IVF outcomes.
METHODS: A comprehensive search was conducted using PubMed, Embase, Scopus, and Web of Science from inception until November 2022. Only English-language publications were included. Inclusion criteria consisted of papers that evaluated genetic biomarkers associated with the cumulus cells (CCs) in humans and the following three outcomes of interest: oocyte quality, embryo quality, and clinical outcomes, including fertilization, implantation, pregnancy, and live birth rates.
RESULTS: The search revealed 446 studies of which 42 met eligibility criteria. Nineteen studies correlated genetic and biochemical biomarkers in CCs with oocyte quality. A positive correlation was reported between oocyte quality and increased mRNA expression in CCs of genes encoding for calcium homeostasis (CAMK1D), glucose metabolism (PFKP), extracellular matrix (HAS2, VCAN), TGF-β family (GDF9, BMP15), and prostaglandin synthesis (PTGS2). Nineteen studies correlated genetic and biochemical biomarkers in CCs with embryo quality. A positive correlation was reported between embryo quality and increased mRNA expression in CCs of genes encoding for extracellular matrix (HAS2), prostaglandin synthesis (PTGS2), steroidogenesis (GREM1), and decreased expression of gene encoding for hormone receptor (AMHR2). Twenty-two studies assessed genetic and biochemical biomarkers in CCs with clinical outcomes. Increased expression of genes encoding for extracellular matrix (VCAN), and TGF-β family (GDF9, BMP15) were positively correlated with pregnancy rate.
CONCLUSIONS: Genetic biomarkers from cumulus cells were associated with oocyte quality (CAMK1D, PFKP, HAS2, VCAN, GDF-9, BMP-15, PTGS2), embryo quality (GREM1, PTGS2, HAS2), and pregnancy rate (GDF9, BMP15, VCAN). These results might help guide future studies directed at tests of cumulus cells to devise objective criteria to predict IVF outcomes.