Reprogenetics, Livingston, NJ, USA.
Reproductive Science Center of New Jersey, Eatontown, NJ, USA.
Hum Reprod. 2017 Apr 1;32(4):743-749. doi: 10.1093/humrep/dex031.
Do external factors affect euploidy in egg donor cycles?
The study demonstrates that during human assisted reproduction, embryonic chromosome abnormalities may be partly iatrogenic.
Chromosome abnormalities have been linked in the past to culture conditions such as temperature and Ph variations, as well as hormonal stimulation. Those reports were performed with older screening techniques (FISH), or ART methods no longer in use, and the subjects studied were not a homogeneous group.
STUDY DESIGN, SIZE, DURATION: A total of 1645 donor oocyte cycles and 13 282 blastocyst biopsies from 42 fertility clinics were included in this retrospective cohort study. Samples from donor cycles with PGS attempted between September 2011 and July 2015 were included.
PARTICIPANTS/MATERIALS, SETTING, METHODS: PGS cycles from multiple fertility clinics referred to Reprogenetics (Livingston, NJ) that involved only oocyte donation were included in this study. Testing was performed by array comparative genomic hybridization (aCGH). Ploidy data were analyzed using Generalized Linear Mixed Models with logistic regression using a logit link function considering a number of variables that represent fixed and random effects.
Euploidy rate was associated with the referring center and independent of almost all the parameters examined except donor age and testing technology. Average euploidy rate per center ranged from 39.5 to 82.5%. The mean expected rate of euploidy was 68.4%, but there are variations in this rate associated with the center effect.
LIMITATIONS, REASONS FOR CAUTION: Data set does not include details of the donor selection process, donor race or ethnic origin, ovarian reserve or ovarian responsiveness. Due to the retrospective nature of the study, associations are apparent, however, causality cannot be established. Discrepancies in regard to completeness and homogeneity of data exist due to data collection from over 40 different clinics.
This is the first study to show a strong association between center-specific ART treatment practices and the incidence of chromosome abnormality in human embryos, although the meiotic or mitotic origin of these abnormalities could not be determined using these technologies. Given the widespread applications of ART in both subfertile and fertile populations, our findings should be of interest to the medical community in general as well as the ART community in particular.
STUDY FUNDING/COMPETING INTEREST(S): No external funds were used for this study. S. Munne is a founding principle of Reprogenetics/current employee of Cooper Genomics. M Alikani's spouse is a founding principle of Reprogenetics/current consultant for Cooper Genomics. The remaining authors have no conflicts to declare.
外部因素会影响卵母细胞捐赠周期中的整倍体吗？
该研究表明，在人类辅助生殖过程中，胚胎染色体异常可能部分是医源性的。
过去已经发现染色体异常与温度和 pH 值变化等培养条件以及激素刺激有关。这些报告是使用较旧的筛选技术（FISH）进行的，或者使用的 ART 方法已不再使用，而且研究的对象不是同质群体。
研究设计、规模、持续时间：这项回顾性队列研究纳入了 42 家生育诊所的 1645 个供卵周期和 13282 个囊胚活检。纳入了 2011 年 9 月至 2015 年 7 月期间进行 PGS 尝试的供卵周期的样本。
参与者/材料、地点、方法：本研究纳入了来自多个生育诊所的仅涉及卵母细胞捐赠的 Reprogenetics（新泽西州利文斯顿）的 PGS 周期。测试通过比较基因组杂交（aCGH）进行。使用广义线性混合模型和逻辑回归分析整倍体数据，使用对数链接函数考虑表示固定和随机效应的多个变量。
整倍体率与参考中心相关，几乎与除供体年龄和检测技术以外的所有检查参数无关。每个中心的平均整倍体率范围为 39.5%至 82.5%。预期的平均整倍体率为 68.4%，但由于中心效应，该比率存在变化。
局限性、谨慎的原因：数据集不包括供体选择过程、供体种族或民族、卵巢储备或卵巢反应性的详细信息。由于研究的回顾性性质，仅显示出明显的关联，但不能确定因果关系。由于从 40 多个不同的诊所收集数据，因此在数据的完整性和同质性方面存在差异。
这是第一项表明中心特异性 ART 治疗实践与人类胚胎染色体异常发生率之间存在强烈关联的研究，尽管使用这些技术无法确定这些异常的减数分裂或有丝分裂起源。鉴于 ART 在不育和生育人群中的广泛应用，我们的研究结果应该引起医学界的广泛关注，特别是 ART 界的关注。
研究资金/利益冲突：本研究没有使用外部资金。S. Munne 是 Reprogenetics 的创始原则/现任员工（现 Cooper Genomics 的员工）。M Alikani 的配偶是 Reprogenetics 的创始原则/现任 Cooper Genomics 的顾问。其余作者没有利益冲突。
