P-115 Clinical prognosis of abnormally cleaved embryos: time-lapse evidence of self-correction before blastulation
Authors: Liu Y , Bickendorf K , Peirce K , Natalwala J , Chapple V 
Published: June 2023

Abstract

Study question
What is the clinical prognosis of embryos displaying abnormal cleavage (ABNCL) observed via time-lapse videography (TLV) and the role of blastulation in embryo self-correction?

Summary answer
ABNCL leads to reduced blastulation rate, but not live birth rates and neonatal outcomes once blastulation has been achieved.

What is known already
It is widely accepted that ABNCL is associated with reduced viability in cleavage stage human embryos. However, evidence is scarce in literature reporting birth outcomes from blastocysts arising from such embryos, mostly because they are ranked low priority for transfer. Knowledge is also limited regarding the potential self-correction mechanism in those leading to live births. In this study, using a large dataset of blastocysts with known live birth outcomes, we aimed to explore the role of blastulation in the self-correction process of ABNCL embryos, and their subsequent live birth rates as well as neonatal outcomes following intrauterine transfer.

Study design, size, duration
This retrospective study involved 1562 consecutive autologous in vitro fertilization cycles (maternal age 35.1 ± 4.7 years) performed at Fertility North between January 2017 and June 2022. Fresh transfers were routinely performed on Day 3 with remaining embryos cultured up to Day 6. A total of 9451 embryos were subject to blastocyst culture, with a subset of 664 resulting blastocysts (following single frozen transfers up to August 2021) included for live birth and neonatal outcome analysis.

Participants/materials, setting, methods
A total of 6019 out of 9451 embryos were annotated for ABNCL up to Day 3, including direct cleavage (DC), reverse cleavage (RC) and &lt;4 intercellular contact points at 4-cell stage (&lt;4ICCP). The remaining 3432 embryos were excluded from TLV annotation due to poor quality as per the 2011 Istanbul consensus. For DC and RC, the number of affected blastomeres was also recorded for the 1st (1-cell), 2nd (2-3-cell), and 3rd cleavage cycles (4-8-cell), respectively.

Main results and the role of chance
Embryos showing DC (19.5%), RC (41.7%), &lt;6ICCP (58.8%), and Mixed (affected by 2 or 3 ABNCL types, 26.4%) had lower blastulation rates than those without ABNCL (67.2%, P &lt; 0.01 respectively). Subgroup analysis showed increasing blastulation rates along cleavage cycles of DC/RC occurrence, from 1st through 2nd to 3rd cleavage cycles (DC 6.3%, 20.7% and 41.0%, P &lt; 0.001; and RC 10.0%, 32.3% and 45.8%, P &lt; 0.05). Negative correlation (P &lt; 0.05 respectively) was also identified between the number of blastomeres affected by DC/RC and subsequent blastulation. However, once blastulation was achieved, clinical results were comparable between blastocysts with DC, RC, &lt;6ICCP and No ABNCL; including live birth rates (25.9%, 33.0%, 36.0% vs 30.8%, P &gt; 0.05 respectively), gestational age (38.7 ± 1.6, 38.5 ± 1.2, 38.3 ± 3.5 vs 38.5 ± 1.8 weeks, P &gt; 0.05 respectively) and birthweight (3343.0 ± 649.1, 3378.2 ± 538.4, 3352.6 ± 841.3 vs 3313.9 ± 509.6 grams, respectively). Above findings held true following multivariate regression (logistic or linear as appropriate); adjusting for maternal age and BMI, vitrification day, blastocyst expansion stage, ICM/TE grades, insemination methods and sperm types. Also, no difference was detected using either Z-score as endpoint combining birthweight, baby sex and gestational age; or preterm delivery (&lt;37 weeks) or low birthweight (&lt;2500 grams) incidences as endpoints. Live-birth embryo TLV indicated self-correction mechanisms by excluding/extruding DC/RC cells before blastulation.

Limitations, reasons for caution
Our study is limited by its retrospective nature, making it impossible to control all known/unknown confounders. Embryos in our dataset, being surplus after selection for those with no or minimum ABNCL for fresh transfer on Day 3, may not represent the full embryo cohort.

Wider implications of the findings
Our findings further support the embryo self-correction mechanism where DC/RC affected blastomere is excluding/extruded at blastulation, which is evidenced by TLV of live-birth embryos. The assuring live birth rates and neonatal outcomes in ABNCL blastocysts provide valuable guidance to clinical practice and patient counselling.

Trial registration number
not applicable