P-175 Morphokinetic growth variance score as a tool to identify euploid embryos with the highest live birth potential
Authors: Bayram A , Elkhatib I , Kalafat E , Abdala A , Ferracuti V , Melado L , Lawrenz B , Fatemi H , Nogueira D 
Published: July 2024

Abstract

Study question
Is the longitudinal growth pattern of euploid embryos associated with live birth rate?

Summary answer
Embryos with lower growth variance score (GVS), i.e., pointing towards a steadier growth during time-lapse monitoring (TLM), have higher live birth rates.

What is known already
Dynamic TLM imaging has been increasingly adopted by fertility clinics as an attempt to improve the ability of selecting embryos with the highest potential for implantation. Many authors have identified and incorporated markers of embryonic morphokinetics into decision algorithms for embryo (de)selection. However, longitudinal changes during this temporal process, and the impact of such changes on embryonic competence remains unknown. Aiming to model the reference ranges of euploid embryonic growth as a single growth trajectory might provide an additive value to blastocyst morphological grade to identify highly competent euploid embryos.

Study design, size, duration
This observational cohort study was performed in a tertiary referral IVF centre between October 2017 and June 2021, including a total of 340 single euploid autologous frozen embryo transfers. Pre-implantation genetic diagnosis for aneuploidy (PGT-A) performed by next generation sequency (NGS). Pregnancy outcomes were assessed as live birth, pregnancy loss or not pregnant.

Participants/materials, setting, methods
Standard morphokinetic parameters (tPB2 to tEB) of all euploid embryos cultured in TLM system were used to develop the reference ranges for the growth variance score (GVS) model. Nuclear errors at two- and four-cell stages, and blastocyst grade before trophectoderm (TE)-biopsy were also annotated. GVS of euploid embryos was evaluated for its association with pregnancy outcomes, and to its predictive ability to live birth potential over TE and inner cell mass (ICM) grade morphology.

Main results and the role of chance
A total of 189 (55.6%) euploid transfers resulted in a live birth, 48 (14.1%) in pregnancy loss and 103 (30. 3%) did not result in pregnancy. The median time for euploid embryo blastulation was 109.9 hours (95% CI:98.8-121.0 hours). Lower quality ICM (OR: 0.13, 95% CI: 0.05-0.33, P &lt; 0.001) and TE (OR: 0.46, 95% CI:0.22-0.94, P = 0.034), multinucleation at 4-cell stage (OR: 0.042, 95% CI:0.21-0.84, P = 0.016) and higher GVS (OR: 0.59, 95% CI: 0.45-0.77, P &lt; 0.001), significantly decreased the odds of live birth. In the multivariable analysis, only GVS (OR: 0.62, 95% CI: 0.46-0.84, P = 0.002) and lower ICM quality (OR: 0.21, 95% CI: 0.06-0.65, P = 0.009) had a significant effect on live birth. There was a significant trend towards higher live birth rates with lower GVS among embryos of similar ICM grades: 85% vs 65% live births in low vs. high GVS for embryos with ICM type A, 76% vs. 48% for ICM type B, 67% vs. 21% for ICM type C, respectively (P for trend &lt;0.001). Addition of the GVS to embryo morphology model (ICM, TE, biopsy day) significantly improved the model’s ability to predict live birth (AUC: 0.67 vs. 0.62, P = 0.015).

Limitations, reasons for caution
The exclusion of IVF cases limits the utility of the model to ICSI-derived embryos. The utility of GVS should be replicated further in external cohorts to confirm its reproducibility in other clinical and laboratory settings.

Wider implications of the findings
By capturing the dynamic growth pattern of embryos, GVS may serve as a valuable tool in prioritizing PGT-A tested embryos for transfer. Its impact was even more prominent for selecting suboptimal blastocysts, which is a more challenging subset of embryos to choose due to their likelihood of reduced viability.

Trial registration number
Not Applicable