Capalbo Antonio, Ottolini Christian S, Griffin Darren K, Ubaldi Filippo Maria, Handyside Alan H, Rienzi Laura
GENERA, Centers for Reproductive Medicine, Rome, Italy; GENETYX, Marostica, Italy.
The Bridge Centre, London, United Kingdom; School of Biosciences, University of Kent, Canterbury, United Kingdom.
Fertil Steril. 2016 Mar;105(3):807-814.e2. doi: 10.1016/j.fertnstert.2015.11.017. Epub 2015 Dec 1.
To study the effect of artificial oocyte activation (AOA) on chromosome segregation errors in the meiotic divisions.
Prospective cohort study with historical control.
Private/academic IVF centers.
PATIENT(S): Fifty-six metaphase II oocytes were donated from 12 patients who had undergone IVF between June 2008 and May 2009.
INTERVENTION(S): Oocytes were activated by 40 minutes' exposure to 100 μM calcium-ionophore. The activated oocyte was tubed and analyzed by array comparative genomic hybridization and/or single-nucleotide polymorphism genotyping and maternal haplotyping (meiomapping). A control sample of embryos derived from normally fertilized oocytes was included for comparison.
MAIN OUTCOME MEASURE(S): Incidence of chromosome segregation errors in artificially activated and normally fertilized oocytes in relation to pronuclear evaluation.
RESULT(S): Of 49 oocytes that survived the warming procedure, thirty-nine (79.6%) activated. Most activated normally, resulting in extrusion of the second polar body and formation of a single or no pronucleus (2PB1PN: 30 of 39, 76.9%; or 2PB0PN: 5 of 39, 12.8%). Twenty-seven of these were analyzed, and 16 (59.3%) were euploid, showing no effect of AOA on meiotic segregation. Single-nucleotide polymorphism analysis of normally activated oocytes confirmed normal segregation of maternal chromosomes. No difference in the proportion of meiosis II type errors was observed between artificially activated oocytes (28.6%; 95% confidence interval 3.7%-71.0%) compared with embryos obtained from normally fertilized oocytes (44.4%; 95% confidence interval 13.7%-78.8%). The abnormally activated oocytes, with ≥2PN (4 of 39, 10.3%) were diploid, indicating a failure to coordinate telophase of meiosis II with polar body extrusion.
CONCLUSION(S): From this preliminary dataset, there is no evidence that AOA causes a widespread increase in chromosome segregation errors in meiosis II. However, we recommend that it be applied selectively to patients with specific indications.
研究人工卵母细胞激活（AOA）对减数分裂中染色体分离错误的影响。
有历史对照的前瞻性队列研究。
私立/学术性体外受精中心。
从2008年6月至2009年5月期间接受体外受精的12名患者捐赠了56个中期II卵母细胞。
将卵母细胞暴露于100μM钙离子载体中40分钟进行激活。激活后的卵母细胞进行体外培养，并通过阵列比较基因组杂交和/或单核苷酸多态性基因分型以及母本单倍型分析（减数分裂图谱分析）。纳入来自正常受精卵母细胞的胚胎作为对照样本进行比较。
人工激活和正常受精卵母细胞中与原核评估相关的染色体分离错误发生率。
在49个经复温程序存活的卵母细胞中，39个（79.6%）被激活。大多数激活正常，导致第二极体排出并形成单个或无原核（2PB1PN：39个中的30个，76.9%；或2PB0PN：39个中的5个，12.8%）。对其中27个进行了分析，16个（59.3%）为整倍体，表明AOA对减数分裂分离无影响。对正常激活卵母细胞的单核苷酸多态性分析证实了母本染色体的正常分离。与从正常受精卵母细胞获得的胚胎（44.4%；95%置信区间13.7%-78.8%）相比，人工激活卵母细胞中减数分裂II型错误的比例无差异（28.6%；95%置信区间3.7%-71.0%）。异常激活的卵母细胞，有≥2个原核（39个中的4个，10.3%）为二倍体，表明减数分裂II末期与极体排出未能协调。
从这个初步数据集来看，没有证据表明AOA会导致减数分裂II中染色体分离错误普遍增加。然而，我们建议有特定指征的患者选择性应用。
