Embryo morphokinetics is potentially associated with clinical outcomes of single-embryo transfers in preimplantation genetic testing for aneuploidy cycles

Reprod Biomed Online. 2019 Oct;39(4):569-579. doi: 10.1016/j.rbmo.2019.05.020. Epub 2019 Jun 6.

Abstract

Research question: Are the morphokinetics of euploid blastocysts evaluated by a generally applicable algorithm associated with the clinical outcomes of single-embryo transfer (SET)?

Design: Time-lapse microscopy was used to compare morphokinetic variables between expanded blastocysts derived from preimplantation genetic testing for aneuploidy cycles using high-resolution next-generation sequencing (hr-NGS). The clinical efficacy of the morphokinetic algorithm KIDScore D5 was evaluated after euploid SET.

Results: Compared with euploid blastocysts, low-level mosaic blastocysts presented comparable morphokinetic and morphological features. However, high-level mosaic blastocysts exhibited significant delays in t5 (median 51.9 h post insemination (hpi), P = 0.034) (where t is the time for the embryo to reach the specific stage in hours after ICSI or conventional IVF) and t8 (median 58.6 hpi, P = 0.032) accompanied by a prolonged time period for the third cell cycle (median 14.7 h, P = 0.012). A significantly higher incidence (P = 0.011) of multinucleation indicated a susceptibility of high-level mosaic blastocysts to mitotic errors. Only a delay in the time for the embryo to reach the full blastocyst stage (median 106.0 hpi, P = 0.039) was revealed in aneuploid blastocysts, reflecting the reduced formation of good-quality blastocysts (42.6% versus 65.7%, P < 0.001). Euploid blastocysts with specific morphokinetic characteristics were graded using the KIDScore D5 algorithm. Grade C embryos achieved significantly lower rates of clinical pregnancy, implantation and ongoing pregnancy (25%, 25% and 10%, respectively) compared with the grade A (76.2%, 79.4% and 68.3%, respectively) or grade B (62.5%, 66.7% and 62.5%, respectively) embryos (P = 0.0171 to <0.0001).

Conclusions: Although morphokinetic features appear dissimilar in embryos with different diploid-aneuploid mosaic levels, predicting chromosomal abnormalities using morphokinetics alone is still insufficient. When combined with hr-NGS, use of the generally applicable KIDScore D5 algorithm has the potential to discriminate euploid blastocysts with different developmental competence.

Keywords: High-resolution next-generation sequencing; Morphokinetics; Preimplantation genetic testing for aneuploidy; Single-embryo transfer; Time-lapse algorithms.

MeSH terms

  • Adult
  • Aneuploidy*
  • Blastocyst / cytology
  • Blastocyst / physiology
  • Cell Shape
  • Cells, Cultured
  • Cleavage Stage, Ovum / cytology
  • Cleavage Stage, Ovum / physiology
  • Embryo Culture Techniques
  • Embryo, Mammalian / cytology*
  • Embryo, Mammalian / diagnostic imaging*
  • Female
  • Fertilization in Vitro
  • Genetic Testing / methods
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Pregnancy
  • Pregnancy Outcome*
  • Preimplantation Diagnosis* / methods
  • Retrospective Studies
  • Single Embryo Transfer* / methods
  • Single Embryo Transfer* / standards
  • Time-Lapse Imaging