Detailed investigation into the cytogenetic constitution and pregnancy outcome of replacing mosaic blastocysts detected with the use of high-resolution next-generation sequencing

Fertil Steril. 2017 Jul;108(1):62-71.e8. doi: 10.1016/j.fertnstert.2017.05.002. Epub 2017 Jun 1.

Abstract

Objective: To determine the pregnancy outcome potential of mosaic embryos, detected by means of preimplantation genetic screening (PGS) with the use of next-generation sequencing (NGS).

Design: Retrospective study.

Setting: Genetics laboratories.

Patient(s): PGS cycles during which either mosaic or euploid embryos were replaced.

Intervention(s): Blastocysts were biopsied and processed with the use of NGS, followed by frozen embryo transfer. Trophectoderm (TE) biopsies were classified as mosaic if they had 20%-80% abnormal cells.

Main outcome measure(s): Implantation, miscarriage rates, and ongoing implantation rates (OIRs) were compared between euploid and types of mosaic blastocysts.

Result(s): Complex mosaic embryos had a significantly lower OIR (10%) than aneuploidy mosaic (50%), double aneuploidy mosaic (45%), and segmental mosaic (41%). There was a tendency for mosaics with 40%-80% abnormal cells to have a lower OIR than those with <40% (22% vs. 56%). However, few embryos (n = 34) with a mosaic error in 40%-80% of the TE sample were replaced. There was no difference between monosomic and trisomic mosaics or between entire chromosome mosaicism or segmental mosaicism. Implantation rates were significantly higher (70% vs. 53%), miscarriage rates lower (10% vs. 25%), and OIRs higher (63% vs. 40%) after euploid embryo transfer than after mosaic embryo transfer.

Conclusion(s): Forty-one percent of mosaic embryos produced an ongoing implantation. Complex mosaic blastocysts had a lower OIR than other mosaics. Mosaic monosomies performed as well as mosaic trisomies and mosaic segmental aneuploidies. The results suggest that embryos with >40% abnormal cells and those with multiple mosaic abnormalities (chaotic mosaics) are likely to have lower OIRs and should be given low transfer priority.

Keywords: Mosaicism; PGD/PGS; next-generation sequencing; pregnancy outcome.

MeSH terms

  • Adult
  • Blastocyst*
  • Cytogenetic Analysis / methods*
  • Embryo Transfer / statistics & numerical data*
  • Female
  • Fertilization in Vitro / statistics & numerical data
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Infertility, Female / epidemiology
  • Infertility, Female / genetics*
  • Infertility, Female / therapy*
  • Mosaicism / embryology*
  • Pregnancy
  • Pregnancy Outcome / epidemiology*
  • Preimplantation Diagnosis
  • Prevalence
  • Reproducibility of Results
  • Retrospective Studies
  • Sensitivity and Specificity
  • Sequence Analysis, DNA
  • Treatment Outcome
  • United States / epidemiology