在单个胚胎移植周期中进行卵丘-卵母细胞复合体基因表达分析结合形态学胚胎评分可提高新鲜胚胎移植后的活产率并缩短妊娠时间。
Cumulus-corona gene expression analysis combined with morphological embryo scoring in single embryo transfer cycles increases live birth after fresh transfer and decreases time to pregnancy.
机构信息
Follicle Biology Laboratory, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090, Brussels, Belgium.
Department of Clinical Biology, Scientific Institute of Public Health, 1050, Brussels, Belgium.
出版信息
J Assist Reprod Genet. 2019 Mar;36(3):433-443. doi: 10.1007/s10815-018-01398-2. Epub 2019 Jan 9.
PURPOSE
Clinical pregnancy rate after IVF with eSET stagnates between 30 and 40%. In order to increase pregnancy and live birth rates, multiple embryo transfer is still common practice. Providing additional non-invasive tools to choose the competent embryo for transfer could avoid multiple pregnancy and improve time to pregnancy. Cumulus mRNA analysis with quantitative PCR (QPCR) is a non-invasive approach. However, so far, no gene sets have been validated in prospective interventional studies.
METHODS
A prospective interventional single-center pilot study with two matched controls (day-3 and day-5 eSET) was performed in 96 patients consenting to the analysis of the cumulus-corona of their oocytes. All patients were super-ovulated for ICSI and eSET at day 3. All oocytes were denuded individually and cumulus was analyzed by quantitative PCR using three predictive genes (EFNB2, SASH1, CAMK1D) and two housekeeping genes (UBC and β2M). Patients (n = 62) with 2 or more day-3 embryos (good or excellent morphology) had their embryo chosen following the normalized expression of the genes.
RESULTS
Corona testing significantly increased the clinical pregnancy and live births rates (63% and 55%) compared to single embryo transfer (eSET) on day 3 (27% and 23%: p < 0.001) and day 5 (43% and 39%: p = 0.022 and p = 0.050) fresh transfer cycle controls with morphology-only selection. Time-to-pregnancy was significantly reduced, regardless of the number of good-quality embryos available on day 3.
CONCLUSION
Combining standard morphology scoring and cumulus/corona gene expression analysis increases day-3 eSET results and significantly reduces the time to pregnancy.
TRIAL REGISTRATION NUMBER
This is not an RCT study and was only registered by the ethical committee of the University Hospital UZBRUSSEL of the Vrije Universiteit Brussel VUB (BUN: 143201318000).
目的
体外受精（IVF）后胚胎种植率（临床妊娠率）停滞在 30%至 40%之间。为了提高妊娠率和活产率，仍然普遍采用多胚胎移植。提供额外的非侵入性工具来选择适合移植的胚胎，可以避免多胎妊娠并缩短妊娠时间。利用实时定量 PCR（qPCR）对卵丘细胞进行 mRNA 分析是一种非侵入性方法。然而，到目前为止，还没有基因集在前瞻性干预研究中得到验证。
方法
本研究是一项前瞻性的、单中心的、有对照的研究，共纳入 96 例患者。所有患者均因接受 ICSI 和第 3 天的 eSET 而同意对卵母细胞的卵丘-卵母细胞复合物进行分析。所有卵母细胞均单独去透明带，然后使用三个预测基因（EFNB2、SASH1、CAMK1D）和两个管家基因（UBC 和β2M）通过 qPCR 对卵丘细胞进行分析。对于有 2 个或更多第 3 天（形态良好或优秀）胚胎的患者，根据基因的归一化表达选择胚胎。
结果
与第 3 天（形态学）单胚胎移植（eSET）（27%和 23%：p<0.001）和第 5 天（形态学）新鲜移植周期对照组（43%和 39%：p=0.022 和 p=0.050）相比，第 3 天的卵丘检测可显著提高临床妊娠率和活产率（分别为 63%和 55%）。无论第 3 天有多少个优质胚胎，妊娠时间均显著缩短。
结论
将标准形态评分与卵丘/卵母细胞基因表达分析相结合，可提高第 3 天 eSET 的结果，并显著缩短妊娠时间。
试验注册号
这不是一项 RCT 研究，仅在布鲁塞尔自由大学UZBRUSSEL 的布鲁塞尔自由大学医院伦理委员会注册（注册号：143201318000）。
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