Day-4 Embryo Defragmentation: Blastocyst Rate and clInical Outcomes

Background: Embryo fragmentation is one of the main morphological parameters assessed during in vitro culture in assisted reproductive technology (ART). The presence of anucleate cytoplasmic fragments is commonly observed in human embryos and may negatively affect developmental potential and clinical outcomes. Embryo defragmentation at early stages (Day 2-3) is an established technique in some centers, but evidence remains heterogeneous. Defragmentation at Day 4 (morula/compaction stage) represents a significantly less explored area, with promising but insufficient data to guide clinical practice. Study Objective: This study aims to evaluate whether mechanical or laser-assisted embryo defragmentation performed on Day 4 (D4) of in vitro culture improves blastocyst development rates and clinical outcomes in ART cycles, compared to standard culture without intervention. Study Design: This is a prospective, randomized controlled trial (RCT) with single-blind assessment. Patients undergoing IVF/ICSI with embryos showing ≥10% fragmentation at D4 morphological evaluation will be randomly assigned (1:1 ratio) to one of two groups: Group A (Intervention): Mechanical/laser defragmentation at D4, followed by standard blastocyst culture Group B (Control): Standard blastocyst culture without any additional manipulation Randomization will be performed at the patient level using pre-generated block randomization lists, stratified by patient age (\50% fragmentation, or severe morphological compromise at Day 3. Primary Outcome: Rate of usable blastocysts (Gardner score ≥3BB) per embryo included in the study, asses