Abstract
Avoiding aneuploid embryo transfers has been shown to improve pregnancy outcomes in patients with implantation failure and pregnancy loss. This retrospective cohort study aims to analyze the correlation of time-lapse (TL)-based variables and numeric blastocyst morphological scores (TLBMSs) with different mosaic levels. In total, 918 biopsied blastocysts with time-lapse assessments at a uniform time-point were subjected to next-generation sequencing–based preimplantation genetic testing for aneuploidy. In consideration of patient- and cycle-related confounding factors, all redefined blastocyst morphology components of low-grade blastocysts, that is, expansion levels (odds ratio [OR] = 0.388, 95% confidence interval [CI] = 0.217–0.695; OR = 0.328, 95% CI = 0.181–0.596; OR = 0.343, 95% CI = 0.179–0.657), inner cell mass grades (OR = 0.563, 95% CI = 0.333–0.962; OR = 0.35, 95% CI = 0.211–0.58; OR = 0.497, 95% CI = 0.274–0.9), and trophectoderm grades (OR = 0.29, 95% CI = 0.178–0.473; OR = 0.242, 95% CI = 0.143–0.411; OR = 0.3, 95% CI = 0.162–0.554), were less correlated with mosaic levels ≤20%, <50%, and ≤80% as compared with those of top-grade blastocysts (p < 0.05). After converting blastocyst morphology grades into scores, high TLBMSs were associated with greater probabilities of mosaic levels ≤20% (OR = 1.326, 95% CI = 1.187–1.481), <50% (OR = 1.425, 95% CI = 1.262–1.608), and ≤80% (OR = 1.351, 95% CI = 1.186–1.539) (p < 0.001). The prediction abilities of TLBMSs were similar for mosaic levels ≤20% (AUC = 0.604, 95% CI = 0.565–0.642), <50% (AUC = 0.634, 95% CI = 0.598–0.671), and ≤80% (AUC = 0.617, 95% CI = 0.576–0.658). In conclusion, detailed evaluation with TL monitoring at the specific time window reveals that redefined blastocyst morphology components and converted numeric TLBMSs are significantly correlated with all of the threshold levels of mosaicism. However, the performance of TLBMSs to differentiate blastocysts with aberrant ploidy risk remains perfectible.
Highlights
The potential confounding variables associated with embryo ploidy were analyzed, including factors related to patient or cycle characteristics, that is female age, anti-Müllerian hormone (AMH), body mass index (BMI), male age, oocyte numbers, mature oocyte numbers, ovarian stimulation protocols, oocyte sources, sperm quality, and artificial insemination methods (ICSI vs. conventional insemination); factors related to the kinetics of blastocoel formation, that is, to accomplish compaction (tM), tSB, tB, tB-tM, and tB-tSB; factors related to embryo dysmorphisms, that is, delayed division (DD), direct cleavage (DC), reverse cleavage (RC), irregular chaotic division (ICD), MN2, and MN4; and factors related to blastocyst morphology, that is, expansion levels, inner cell mass (ICM) quality, and TE quality
Data revealed that female age was associated with mosaic levels ≤20%; female age, mature oocyte numbers, and oocyte sources were significantly associated with mosaic levels
The results demonstrated that a higher rate of high-level mosaicism was observed in the good morphology blastocysts (TLBMSs ≥6) with MN4 (20%) than the good morphology blastocysts without MN4 (9.3%) (p < 0.05), suggesting deselection of MN4 embryos could be considered to reduce the risk of selecting good morphology blastocysts with highlevel mosaicism (Supplementary Figure S2D)
Summary
Several studies have suggested that time-lapse (TL) monitoring can enhance aneuploid embryo identification, based on blastulation kinetics (Campbell et al, 2013a; Campbell et al, 2013b; Basile et al, 2014; Minasi et al, 2016; Del Carmen Nogales et al, 2017; Mumusoglu et al, 2017; Desai et al, 2018). Using TL technology, dynamic dysmorphisms of cleavage-stage embryos, such as multinucleation (MN), reverse cleavage (RC), irregular chaotic division (ICD), or direct cleavage (DC), can be evaluated in more detail, and two or more dysmorphisms are correlated with a reduced euploidy probability (Desai et al, 2018). These studies have determined the ploidy status, at least in part if not all, of the biopsied embryos through array comparative genomic hybridization (aCGH), which has insufficient sensitivity for the detection of diploid–aneuploid mosaicism (van EchtenArends et al, 2011; Munne and Wells 2017; Sachdev et al, 2017)
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