Early embryo morphokinetics is a better predictor of post-ICSI live birth than embryo morphology: speed is more important than beauty at the cleavage stage

Abstract

Given the importance of embryo developmental competence assessment in reproductive medicine and biology, the aim of this study was to compare the performance of fertilization and cleavage morphokinetics with embryo morphology to predict post-ICSI live birth. Data from embryos cultured in a time-lapse microscopy (TLM) incubator and with known live birth outcomes (LB: embryos achieving live birth, n = 168; NLB: embryos not achieving live birth, n = 1633) were used to generate receiver operating characteristic (ROC) curves based on morphokinetic or morphological scores, and the respective areas under the curve (AUC) were compared. The association between live birth and 12 combinations of four morphokinetic quality degrees (A–D) with three morphological quality degrees (A–C) was assessed using multivariate analysis. Morphokinetic parameters from tPNa to t8 were reached earlier in LB compared with NLB embryos. The ROC curve analysis indicated that morphokinetic information is more accurate than conventional morphology to predict live birth [AUC = 0.64 (95% CI 0.58–0.70) versus AUC = 0.58 (95% CI 0.51–0.65)]. The multivariate analysis was in line with AUCs, revealing that embryos with poor morphokinetics, independently of their morphology, provide lower live birth rates (P < 0.001). A considerable percentage of embryos with top morphology presented poor morphokinetics (20.10%), accompanied by a severely reduced live birth rate in comparison with embryos with top morphology and morphokinetics (P < 0.001). In conclusion, TLM-derived early morphokinetic parameters were more predictive of live-birth achievement following ICSI than conventional morphology.

Faster Fertilization and Cleavage Kinetics Reflect Competence to Achieve a Live Birth: Data from Single-Embryo Transfer Cycles

“…Faster tPNf and t2 are believed to be related to embryo morphology on the third day [7]; however, this is not always the case. There are reports that early embryo morphokinetics are better predictors of post-ICSI live births than embryo morphology [6]. Earlier t3, t4, and t5 are related to higher implantation rates, whereas t4 reflects the quality of blastocysts [12,35].…”

“…However, among embryos with appropriate morphology, a considerable proportion (20.1%) showed poor kinetic parameters, accompanied by a severely reduced live birth rate (P < 0:001). Compared to traditional morphology, early morphological dynamics can predict live births more accurately [6]. This indicates that early embryonic morphological dynamics can be used as an important parameter for embryo selection and transfer.…”

“…Numerous studies show that faster developmental kinetics are related to higher cell numbers [6,7], better blastocyst formation [8][9][10][11], and higher implantation [12,13] and pregnancy rates [4,14]. Although these studies provide a theoretical basis for developing TLI-based embryo selection algorithms aimed at improving implantation and pregnancy rates [15][16][17], investigation of the impact on live birth rates needs to be performed [18].…”

Paternal periconception metabolic health and offspring programming

“…Furthermore, these embryos demonstrated an impaired ability to achieve developmental milestones in vitro and ultimately failed to achieve blastocyst expansion at an appropriate time-point (37) . Early embryo cleavage dynamics have been associated with rates of ongoing development and live birth within clinical ART settings (38) . Recently, the association between being overweight in men and a reduction in fertility has been supported further through a large-scale meta-analysis of 115 158 study participants, revealing obese men had an increased likelihood of infertility (39) .…”

Development of a dynamic machine learning algorithm to predict clinical pregnancy and live birth rate with embryo morphokinetics

“…To obtain objective, real-time embryo morphologic data with potential clinical relevance, we focused on time-lapse microscopy as a noninvasive method to characterize embryo quality. Many studies have identified parameters associated with improved clinical outcomes, including time of appearance and fading of two pronuclei ( 9 ), the timing of cell cycle events ( 10 , 11 ), the time between 2- to the 8-cell cleavage stage ( 12 , 13 , 14 , 15 ), cleavage events ( 16 ), cytokinesis duration ( 17 ), time to initiation of blastulation ( 18 , 19 , 20 ), and combined morphokinetic and morphologic or molecular parameters ( 21 , 22 , 23 , 24 , 25 , 26 , 27 ). Other studies showed that no differences were found in the time-lapse parameters of euploid embryos that led to miscarriages ( 28 ).…”