使用PGD偵測胚胎染色體正常植入仍然流產之原因在於部分胚胎之染色體呈現異常(31.6% were mosaic and 5.2% were polyploid )

結論: 目前傳統PGD aCGH偵測無法百分之百準確，偵測染色體正常仍有部分胚胎之染色體呈現異常(mosaicism, polyploid)

Fertil Steril. 2016 Sep 27. pii: S0015-0282(16)62686-9. doi: 10.1016/j.fertnstert.2016.08.017. [Epub ahead of print]

Why do euploid embryos miscarry? A case-control study comparing the rate of aneuploidy within presumed euploid embryos that resulted in miscarriage or live birth using next-generation sequencing.

Maxwell SM1, Colls P2, Hodes-Wertz B3, McCulloh DH3, McCaffrey C3, Wells D4, Munné S2, Grifo JA3.

Author information

Abstract

OBJECTIVE:

To determine whether undetected aneuploidy contributes to pregnancy loss after transfer of euploid embryos that have undergone array comparative genomic hybridization (aCGH).

DESIGN:

Case-control study.

SETTING:

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.