Perturbations of morphogenesis at the compaction stage affect blastocyst implantation and live birth rates

• Published in: Human reproduction (Oxford) 2021-03, Vol.36 (4), p.918-928
• Main Authors: Coticchio, Giovanni, Ezoe, Kenji, Lagalla, Cristina, Shimazaki, Kiyoe, Ohata, Kazuki, Ninomiya, Maya, Wakabayashi, Natsuki, Okimura, Tadashi, Uchiyama, Kazuo, Kato, Keiichi, Borini, Andrea
• Format: Article
• Language: English
• ISSN: 0268-1161; 1460-2350
• DOI: 10.1093/humrep/deab011

Abstract STUDY QUESTION Do perturbations of embryo morphogenesis at compaction affect blastocyst development and clinical outcomes in assisted reproduction cycles? SUMMARY ANSWER Cell exclusion and extrusion, i.e. cell disposal occurring respectively before or during morula compaction, affect blastocyst yield and quality, as well as rates of pregnancy and live birth. WHAT IS KNOWN ALREADY Despite its pivotal role in morphogenesis for blastocyst organisation and cell fate determination, compaction at the morula stage has received little attention in clinical embryology. Time lapse technology (TLT) allows detailed morphokinetic analysis of this developmental stage. However, even in the vast majority of previous TLT studies, compaction was investigated without a specific focus. Recently, we reported that compaction may be affected by two clearly-distinct patterns of cell disposal, exclusion and extrusion, occurring prior to and during compaction, respectively. However, the crucial question of the specific relevance of partial compaction for embryo development and competence in ART has remained unanswered until now. STUDY DESIGN, SIZE, DURATION This study involved the assessment of laboratory and clinical outcomes of 2,059 morula stage embryos associated with 1,117 ICSI patients, who were treated with minimal stimulation and single vitrified-warmed blastocyst transfer (SVBT) from April 2017 to March 2018. Patterns of morula compaction were assessed and analyzed in relation to embryonic and clinical outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS Following ICSI, time-lapse videos were analysed to annotate morphokinetic parameters relevant to both pre- and post-compaction stages. According to their morphokinetic history, morulae were classified as: (I) fully compacted morulae (FCM); (II) partially compacted morulae (PCM), showing cells (a) excluded from the compaction process from the outset (Exc-PCM), (b) extruded from an already compacted morula (Ext-PCM), or (c) showing non-compacted cells arisen from both patterns (Exc/Ext-PCM). The number of excluded/extruded cells was also annotated. Possible correlations of compaction patterns with 13 morphokinetic parameters, abnormal cleavage, blastocyst yield and morphological grade, clinical and ongoing pregnancy rates, and live birth rate were evaluated. Other factors, such as patient and cycle characteristics, possibly associated with compaction patterns and their outcomes, were investigated. MAIN RESULTS AND THE