P-181 Chromosome constitution and clinical outcome of blastocysts derived from morulae with different compaction patterns
Authors: Lagalla C , Zacà C , Tarozzi N , Borini A , Cimadomo D , Rienzi L , Coticchio G 
Published: July 2024

Abstract

Study question
Do blastocysts with a diverse history of compaction pattern (complete or partial) have different chances to be aneuploid and to implant?

Summary answer
Embryos undergoing partial or complete compaction have comparable chances to be aneuploid. Euploid blastocysts with previous history of blastomere extrusion have reduced chances of implantation.

What is known already
Compaction at the morula stage is an essential requisite for blastocyst formation and involves blastomere flattening and establishment of tenacious cell-to-cell contacts. Incomplete compaction is associated with several upstream and downstream morphokinetic anomalies. It also affects blastocyst yield and quality and clinical outcome. However, evidence on blastocyst chromosomal constitution and implantation potential after preimplantation genetic testing for aneuploidies (PGT-A) is lacking.

Study design, size, duration
This retrospective cohort study assessed laboratory and clinical outcomes of 1206 blastocysts derived from 483 infertile patients undergoing ART treatment and PGT-A from January 2015 to July 2022. Three age groups (≤34, 35–38 and ≥39 years) were adopted for sub-analyses. Biopsied blastocysts were vitrified and subsequently used in single vitrified-warmed blastocyst transfers (SVBT).

Participants/materials, setting, methods
Embryo development was monitored by time-lapse technology (TLT), also annotating abnormal cleavages and multinucleation. Patterns of morula compaction were assessed according to previously published categories: (i) full compaction, with all blastomeres undergoing compaction (FCM); partial compaction (partially compacted morula [PCM]), with (ii) blastomeres excluded from the outset (exc-PCM) or (iii) extruded after start of compaction (ext-PCM). Embryos were assessed in relation to embryonic and clinical outcomes. PGT-A data were obtained from trophectoderm biopsies.

Main results and the role of chance
Average maternal age of the overall patient population was 39.0 years. The full compaction pattern (FCM) was detected in 35.7% of all embryos. Partially compacted morulae showing excluded (Exc-PCM) or extruded (Ext-PCM) cells were also observed (54.4% and 9.9%, respectively) and collectively (64.3%) were the larger fraction (P &lt; 0.0001, among all groups). Of 1206 analysed blastocysts, 551 were euploid, of which 366 were used in SVBT. Aneuploidy rate in the overall blastocyst population derived from FCM, Exc-PCM and Ext-PCM was 50.8%, 55.6%, and 60.0%, respectively (P &gt; 0.05). However, in the younger maternal age group (≤34 years), the aneuploidy rate of the Exc-PCM group was higher compared with FCM (39.8% vs. 25.3%, P = 0.03). In the overall population, the Ext-PCM phenotype was associated with a lower implantation rate (FCM, Exc-PCM and Ext-PCM:47.8%, 44.7%, 55.6%, and 27,6%, respectively (P = 0.04), while miscarriage rates were comparable. Finally, transferred euploid blastocysts not classified according to maternal age implanted with comparable rates, irrespective of their morphokinetic history (abnormal division, multinucleation, no morphokinetic abnormalities).

Limitations, reasons for caution
The study is limited by its retrospective design. Having been obtained from a single centre, the data require independent validation

Wider implications of the findings
This study confirms and extends our previous findings on the implications of partial compaction. Importantly, it further consolidates the notion that the embryo can develop through atypical morphokinetic patterns while often preserving its genomic integrity and implantation ability.

Trial registration number
Not applicable