Maxwell Susan M, Colls Pere, Hodes-Wertz Brooke, McCulloh David H, McCaffrey Caroline, Wells Dagan, Munné Santiago, Grifo James A
New York University Langone Medical Center, New York University Fertility Center, New York, New York.
Reprogenetics, Livingston, New Jersey.
Fertil Steril. 2016 Nov;106(6):1414-1419.e5. doi: 10.1016/j.fertnstert.2016.08.017. Epub 2016 Sep 28.
To determine whether undetected aneuploidy contributes to pregnancy loss after transfer of euploid embryos that have undergone array comparative genomic hybridization (aCGH).
Case-control study.
University-based fertility center.
PATIENT(S): Cases included 38 patients who underwent frozen euploid ET as determined by aCGH, resulting in miscarriage. Controls included 38 patients who underwent frozen euploid ET as determined by aCGH, resulting in a live birth.
INTERVENTION(S): Next-generation sequencing (NGS) protocols were internally validated. Saved amplified DNA samples from the blastocyst trophectoderm biopsies previously diagnosed as euploid by aCGH were reanalyzed using NGS. Cytogenetic reports of the products of conception for 20 of the pregnancies resulting in miscarriage were available for comparison.
MAIN OUTCOME MEASURE(S): The incidence of aneuploidy and mosaicism using NGS within embryos resulting in miscarriage and live birth.
RESULT(S): Of euploid embryos analyzed by aCGH resulting in miscarriage, 31.6% were mosaic and 5.2% were polyploid by NGS. The rate of chromosomal abnormalities was significantly higher in embryos resulting in miscarriage (36.8%) than in those resulting in live births (15.8%). The rate of mosaicism was twice as high among embryos resulting in miscarriage than those resulting in live birth, but this was not statistically significant. Next-generation sequencing detected more cases of mosaicism than cytogenetic analysis of products of conception.
CONCLUSION(S): Undetected aneuploidy may increase the risk of first trimester pregnancy loss. Next-generation sequencing may detect mosaicism and triploidy more frequently than aCGH, which could help to identify embryos at high risk of miscarriage. Mosaic embryos, however, should not be discarded as some can result in live births.
确定未检测到的非整倍体是否会导致经阵列比较基因组杂交（aCGH）检测为整倍体的胚胎移植后发生流产。
病例对照研究。
大学附属生育中心。
病例组包括38例经aCGH检测为整倍体的冷冻胚胎移植后发生流产的患者。对照组包括38例经aCGH检测为整倍体的冷冻胚胎移植后分娩活婴的患者。
对新一代测序（NGS）方案进行内部验证。使用NGS对先前经aCGH诊断为整倍体的囊胚滋养外胚层活检保存的扩增DNA样本进行重新分析。可获得20例流产妊娠的妊娠产物的细胞遗传学报告以供比较。
通过NGS检测流产和分娩活婴的胚胎中非整倍体和嵌合体的发生率。
经aCGH分析为整倍体但导致流产的胚胎中，31.6%为嵌合体，5.2%为多倍体。导致流产的胚胎染色体异常率（36.8%）显著高于分娩活婴的胚胎（15.8%）。导致流产的胚胎中嵌合体发生率是分娩活婴胚胎的两倍，但差异无统计学意义。新一代测序检测到的嵌合体病例比妊娠产物的细胞遗传学分析更多。
未检测到的非整倍体可能会增加孕早期流产的风险。新一代测序可能比aCGH更频繁地检测到嵌合体和三倍体，这有助于识别流产风险高的胚胎。然而，不应丢弃嵌合胚胎，因为有些嵌合胚胎可以分娩活婴。
