Spontaneous collapse as a prognostic marker for human blastocysts: a systematic review and meta-analysis

Abstract

STUDY QUESTION Is spontaneous collapse (SC) by human blastocysts a prognostic factor in IVF treatment? SUMMARY ANSWER SC in human blastocyst is associated with reduced euploid embryo and pregnancy rates. WHAT IS KNOWN ALREADY SC of the human blastocyst is a phenomenon that was revealed relatively recently following the clinical application of time-lapse monitoring in IVF laboratories. The ploidy and clinical prognosis of affected blastocysts are still poorly understood, with inconsistent reports. Systematic reviews and meta-analyses on this topic are currently absent in the literature but its potential as a marker of embryo viability holds great clinical value. In this study, we aimed to comprehensively evaluate the potential of SC as a prognostic factor in regard to ploidy status, and pregnancy, live birth and miscarriage rates. STUDY DESIGN, SIZE, DURATION A systematic review and meta-analysis were performed according to PRISMA guidelines, with a protocol registered with PROSPERO (CRD42022373749). A search of MEDLINE, EMBASE, and the Cochrane Library for relevant studies was carried out on 10 October 2022, using key words relevant to ‘blastocyst collapse’ and ‘time-lapse imaging’. PARTICIPANTS/MATERIALS, SETTING, METHODS Two independent reviewers systematically screened and evaluated each study in terms of participants, exposure, comparator, and outcomes (PECO). The Quality In Prognosis Studies tool was used for quality assessment. Data were extracted according to Cochrane methods. Pregnancy, live birth, ploidy, or miscarriage data were summarized by risk ratios (RRs) or odds ratios and their 95% CIs. All meta-analyses were performed with random-effects models. MAIN RESULTS AND THE ROLE OF CHANCE Following removal of duplicates, a total of 196 records were identified by the initial search. After screening according to PECO, 19 articles were included for further eligibility assessment. For meta-analysis, seven retrospective cohort studies were eventually included. After data pooling, the incidence of blastocyst SC was 37.0% (2516/6801) among seven studies (ranging from 17.4% to 56.2%). SC was associated with significantly lower clinical pregnancy rates (two studies, n = 736; RR = 0.77, 95% CI = 0.62–0.95; I2 = 30%), ongoing pregnancy rates (five studies, n = 2503; RR = 0.66, 95% CI = 0.53–0.83; I2 = 60%), and reduced euploidy rates (three studies, n = 3569; RR = 0.70, 95% CI = 0.59–0.83; I2 = 69%). Nevertheless, live birth rates (two studies, n = 816; RR = 0.76, 95% CI = 0.55–1.04; I2 = 56%) and miscarriage rate (four studies, n = 1358; RR = 1.31, 95% CI = 0.95–1.80; I2 = 0%) did not differ between blastocysts with or without SC. There was, however, significant heterogeneity between the studies included for evaluation of ongoing pregnancy rates (I2 = 60%, P = 0.04), live birth rates (I2 = 56%, P = 0.13), and ploidy rates (I2 = 69%, P = 0.04). Subgroup analyses were conducted according to different definitions of SC, number of collapse events, and whether the transferred blastocyst had undergone preimplantation genetic testing for aneuploidy; with inconclusive findings across subgroups. LIMITATIONS, REASONS FOR CAUTION All studies in the meta-analysis were retrospective with varying levels of heterogeneity for different outcomes. Not all studies had accounted for potential confounding factors, therefore only unadjusted data could be used in the main meta-analysis. Studies employed slightly different strategies when defining blastocyst SC. Standardization in the definition for SC is needed to improve comparability between future studies. WIDER IMPLICATIONS OF THE FINDINGS Our results indicate that blastocyst SC has negative implications for a pregnancy. Such blastocysts should be given a low ranking when selecting from a cohort for intrauterine transfer. Blastocyst SC should be considered as a contributing variable when building blastocyst algorithms to predict pregnancy or live birth. STUDY FUNDING/COMPETING INTEREST(S) There is no external funding to report. All authors report no conflict of interest. REGISTRATION NUMBER PROSPERO 2022 CRD42022373749

Developmental perturbation in human embryos: Clinical and biological significance learned from time‐lapse images

“…Blastocyst spontaneous collapses and the frequency of these occurrences are associated with degeneration before full expansion, delayed development, reduced morphological quality, and higher rates of aneuploidy. 153 , 173 Additionally, blastocyst transfer results in poor pregnancy outcomes. 170 , 172 , 173 , 174 Blastocysts without spontaneous collapse should be prioritized for transfer.…”

A brief history of artificial intelligence embryo selection: from black-box to glass-box

“…The clinical introduction of TLV offers potentially decreased inter-operator subjectivity in the annotation step in comparison to static observation ( Scott et al , 2021 ), while also enabling identification of novel viability biomarkers ( Liu et al , 2020b ; Bickendorf et al , 2023 ). Compared to static morphology, the subjectivity of the ranking step in traditional embryo selection using TLV can be further reduced by use of an algorithm with a defined set of rules to determine the most viable embryo.…”

“…Commercial algorithms may benefit from access to larger datasets so that a more balanced transferability/performance can be achieved, though large high-quality datasets are difficult to obtain ( Hickman et al , 2020 ). There are, however, alternative paths to address the transferability issue by utilizing more transferable qualitative TLV measures, such as abnormal cleavage ( Liu et al , 2020a ) or spontaneous blastocyst collapse ( Bickendorf et al , 2023 ). Annotation for embryo abnormal cleavage patterns is still mostly performed manually by an embryologist, while newer reports, such as on blastocyst spontaneous collapse ( Cimadomo et al , 2022 ), are starting to engage AI-powered tools to enable automated annotation.…”

Exploring the Impact of Controlled Ovarian Stimulation and Non-Invasive Oocyte Assessment in ART Treatments

“…The application of time-lapse systems could be considered as a valuable approach to reduce the inter-variation between operators and provides a better evaluation of fertilization, cyto-dynamics, cell division, morula and blastocyst formation, which can be adopted as a noninvasive assessment. In addition, continuous evaluation of embryo development allows to discriminate those abnormal phenotypes that otherwise would be less frequently observed during standard culture, including abnormal cleavage, reverse cleavage, multinucleation and blastocyst collapse events, just to mention some [116][117][118][119][120][121]. Furthermore, the application of novel generations of microscopies, such as polarized microscopy, hyperspectral microscopy and Raman microspectroscopy (RM), will be valuable to assess not only the metabolic state of the embryo but also to understand more about early embryo assessment and implantation potential [100].…”