Time-lapse imaging reveals delayed development of embryos carrying unbalanced chromosomal translocations

Abstract

Purpose: The purpose of the study was to compare the morphokinetic parameters of embryos carrying balanced chromosomal translocations with those carrying unbalanced chromosomal translocations using time-lapse microscopy.

Methods: The study group included 270 embryos that underwent biopsies on day 3 for preimplantation genetic diagnosis (PGD) for chromosomal translocations in our unit between 2013 and 2015. All embryos were incubated under time-lapse microscopy and evaluated for timing of developmental events up to day 5. The timing of these events was compared between balanced and unbalanced embryos, potentially viable and nonviable variants, and maternal versus paternal inheritance of the translocation.

Results: The PGD analysis found that 209 (77%) of the 270 biopsied embryos carried an unbalanced translocation. Embryos carrying unbalanced translocations, which are expected to lead to implantation failure or miscarriage, cleaved less synchronously and were delayed in time of cleavage to the 4-cell stage (t4) and in time of start of blastulation (tSB) compared with balanced embryos (P < 0.05). Furthermore, embryos carrying nonviable translocations demonstrated a significant delay at the time of pronuclei fading (tPNf) compared with those carrying potentially viable translocations (P < 0.05). Embryos whose unbalanced translocations were of maternal origin were significantly delayed in most of the morphokinetic parameters (including tPNf, t2, t3, t4, t6, t7, t8, cc2, s2, and tSB) compared with embryos carrying balanced translocations (P < 0.05).

Conclusions: Embryos carrying unbalanced chromosomal translocations mainly of maternal origin undergo delayed development and asynchronous cleavage that may lead to implantation failure or miscarriage.

Keywords: Chromosomal translocations; Morphokinetic parameters; Preimplantation development; Time-lapse imaging.

Fig. 1

Flowchart showing the formation of the study group. The original group included 593 embryos from 89 cycles that underwent PGD-FISH for chromosomal translocations. The final study group for all analyses included 270 biopsied embryos from 48 cycles. Comparisons between balanced and unbalanced embryos, potentially viable and nonviable variants, and parental inheritance were performed by means of time-lapse technology

Fig. 2

Comparison between the distribution of time-lapse morphokinetic parameters of embryos carrying balanced and unbalanced translocation: t4 = time (h) between ICSI and the four-cell stage; s2 = synchrony (h) in the division from three to four cells; initiation of blastulation (tSB) defined by time (h) between ICSI and initiation of blastulation. The mean (for t4 and tSB) and median (for s2) values are indicated by red dots. *P < 0.05

Fig. 3

Comparison between the distribution of time-lapse morphokinetic parameters of potentially viable and nonviable embryos. Pronuclei fading (tPNf) = time (h) between ICSI and pronuclei fading; t4 = time (h) between ICSI and the four-cell stage; initiation of blastulation (tSB) defined by time (h) between ICSI and initiation of blastulation. The mean values are indicated by red dots. *P < 0.05, **P < 0.01