Emory Reproductive Center, Emory University School of Medicine, Atlanta, GA.
Fertility and Reproductive Medicine Center, Washington University School of Medicine, St Louis, MO.
Am J Obstet Gynecol. 2018 Dec;219(6):602.e1-602.e7. doi: 10.1016/j.ajog.2018.09.030. Epub 2018 Sep 29.
The growing use of preimplantation genetic testing with in vitro fertilization has provided clinicians with more information about the genetics of embryos. Embryos, however, sometimes result with a mixed composition of both aneuploid and euploid cells, called mosaic embryos. The interpretation of these results has varied, leading some clinicians to transfer mosaic embryos and some opt not to. In addition, laboratories providing preimplantation genetic testing for aneuploidy have differing thresholds for determining an embryo aneuploid, mosaic, or euploid. Overall practice patterns for mosaic embryo transfer practices in the United States are unknown.
OBJECTIVE(S): The objectives of the study were to characterize national mosaic embryo transfer practices, including the use of preimplantation genetic testing for aneuploidy, prior history of transferring mosaic embryos, thresholds for determining mosaicism, and willingness to transfer mosaic embryos among assisted reproductive technology clinics in the United States.
A 14 question online survey assessing current use of preimplantation genetic testing for aneuploidy, thresholds for determining mosaicism, and clinic experience and willingness to transfer mosaic embryos was e-mailed to 405 assisted reproductive technology clinics across the United States. Descriptive statistics and logistic regression were used to analyze survey responses and identify clinical factors associated with reporting having ever transferred a mosaic embryo.
Of the 405 US assisted reproductive technology clinics contacted, 252 (62.2%) completed a survey, including 157 private (62.3%), 55 academic (21.8%), and 40 hybrid (15.9%) clinics. Most clinics (168, 66.7%) reported conducting preimplantation genetic testing for aneuploidy on less than 50% of all in vitro fertilization cycles. The most common type of preimplantation genetic testing for aneuploidy technology used was next-generation sequencing at 88.9%. Ninety-one clinics (36.1%) receive mosaicism data on their preimplantation genetic testing for aneuploidy report; the most common thresholds for determining embryo aneuploidy and euploidy by clinics' primary genetics laboratories were <20% normal (36.3%) and >80% normal (46.2%), respectively. Thirty-nine (42.9%) of the 91 have transferred and 57 (62.6%) would transfer a mosaic embryo. Nearly 40% of clinics were unsure about their thresholds for mosaic transfer and one fourth of clinics reported they had no threshold. Private (odds ratio, 1.0, 95% confidence interval, 0.5-1.8) and hybrid (odds ratio, 0.9, 95% confidence interval, 0.4-2.1) clinics were just as likely as academic clinics to report having transferred a mosaic embryo. Clinics in the northeastern United States were more likely to have transferred a mosaic embryo than clinics in other regions (odds ratio, 1.5, 95% confidence interval, 0.9-2.7). Most clinics (72.6%) report they do not have a unique consent for transfer of mosaic embryos.
There is uncertainty and variability in the transfer practices of mosaic embryos and classification of mosaicism among US assisted reproductive technology clinics. These findings provide an opportunity to establish mosaicism thresholds and create standardized guidelines for transferring mosaic embryos.
体外受精中胚胎植入前遗传学检测的应用日益广泛,为临床医生提供了更多关于胚胎遗传学的信息。然而,胚胎有时会出现染色体数目异常和正常细胞混合的情况,称为嵌合体胚胎。这些结果的解释各不相同,一些临床医生选择移植嵌合体胚胎,而另一些则选择不移植。此外,提供胚胎植入前遗传学检测非整倍体的实验室对于确定胚胎非整倍体、嵌合体或整倍体的阈值也有所不同。美国对于嵌合体胚胎移植的整体实践模式尚不清楚。
本研究的目的是描述美国全国范围内的嵌合体胚胎移植实践,包括使用胚胎植入前遗传学检测非整倍体、既往移植嵌合体胚胎的历史、确定嵌合体的阈值以及辅助生殖技术诊所对移植嵌合体胚胎的意愿。
一项针对当前使用胚胎植入前遗传学检测非整倍体、确定嵌合体的阈值以及诊所经验和移植嵌合体胚胎意愿的 14 个问题的在线调查通过电子邮件发送给美国 405 家辅助生殖技术诊所。采用描述性统计和逻辑回归分析来分析调查结果,并确定与报告曾移植过嵌合体胚胎相关的临床因素。
在联系的 405 家美国辅助生殖技术诊所中,有 252 家(62.2%)完成了调查,其中包括 157 家私立(62.3%)、55 家学术(21.8%)和 40 家混合(15.9%)诊所。大多数诊所(168 家,66.7%)报告称,他们对不到 50%的体外受精周期进行了胚胎植入前遗传学检测非整倍体检测。使用最广泛的胚胎植入前遗传学检测非整倍体技术是下一代测序,占 88.9%。91 家诊所(36.1%)在其胚胎植入前遗传学检测非整倍体报告中收到了嵌合体数据;诊所主要遗传学实验室确定胚胎非整倍体和整倍体的最常见阈值分别为<20%正常(36.3%)和>80%正常(46.2%)。其中 39 家(42.9%)曾移植过嵌合体胚胎,57 家(62.6%)愿意移植嵌合体胚胎。近 40%的诊所对其嵌合体移植阈值不确定,四分之一的诊所报告称他们没有阈值。私立(优势比,1.0,95%置信区间,0.5-1.8)和混合(优势比,0.9,95%置信区间,0.4-2.1)诊所与学术诊所一样,有同样的可能性报告曾移植过嵌合体胚胎。与其他地区相比,美国东北部地区的诊所更有可能移植过嵌合体胚胎(优势比,1.5,95%置信区间,0.9-2.7)。大多数诊所(72.6%)报告称,他们没有用于移植嵌合体胚胎的独特同意书。
美国辅助生殖技术诊所对于嵌合体胚胎的移植实践和嵌合体的分类存在不确定性和差异。这些发现为确定嵌合体阈值和制定移植嵌合体胚胎的标准化指南提供了机会。