Impact of early cleaved zygote morphology on embryo development and in vitro fertilization-embryo transfer outcome: a prospective study

APHP, Departments of Biology and Genetics of Reproduction, Antoine Béclère Hospital, Clamart, France.
Fertility and sterility (Impact Factor: 4.59). 07/2008; 89(6):1677-84. DOI: 10.1016/j.fertnstert.2007.04.047
Source: PubMed


To evaluate the impact of the first division morphology on embryo development and IVF-embryo transfer outcome.
Prospective study.
Teaching hospital, France.
All zygotes from 201 couples were checked for early cleavage. We defined as "even," early cleaved (EC) zygotes with 2 cells of even size; as "uneven," EC zygotes with 2 cells of uneven size; and as "fragmented," EC zygotes with more than 20% fragmentation rate. Day 2 embryo quality was assessed as "top" embryo or "non-top," with the evaluation of multinucleated blastomeres.
Day 2 embryo quality, pregnancy and implantation rates.
Among EC zygotes, 59.1% were even, 13.0% were uneven, and 27.9% were fragmented. Even EC yielded more "top" embryos and less multinucleated blastomere embryos than uneven EC (77.0% vs. 46.3%) and fragmented EC (77.0% vs. 13.9%). The 125 double embryo transfers that comprised at least one embryo derived from even EC zygote led to higher pregnancy rate (PR) (64.0% vs. 43.4%) and implantation rate (42.0% vs. 27.6%) compared to the 76 double embryo transfers with embryos derived from breakdown or 2PN zygotes.
The morphology of the early cleaved zygote is involved in embryo development. Evaluation of this morphology is an effective and valuable method of assessing the embryo quality.

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    • "Nevertheless, numerous other studies have failed to show that the addition of PN scoring to a cumulative scoring system can effectively improve the selection of viable embryos (reviewed by Skiadas and Racowsky, 2007). Uneven cleavage is supposed to negatively affect the developmental capacity of the embryo (Hesters et al., 2008; Scott et al., 2007) and has been correlated with multinucleation and aneuploidy due to failures in chromosomal replication (Hardarson et al., 2001). The occurrence of multinucleation, which is defined by the presence of more than one nucleus in at least one blastomere of the embryo in an early cleavage stage, is also associated with impaired developmental capacity (Van Royen et al., 2003; Yakin et al., 2005). "
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    ABSTRACT: Time-lapse imaging is increasingly applied as an adjunct to reproductive medicine. The gained information of the morphological and morphokinetic variables before the onset of transcription are supposed to be good predictors for the selection of the best embryo for transfer and are often seen in line with clinical outcomes. This retrospective case series investigated the outcome of transferred blastocysts that did not fulfil the proposed embryo scores at early cleavage or at later stages of development. The observations were made by time-lapse imaging. This study reports the birth of 16 healthy children after day-5 blastocyst transfer, of which at least one of the transferred embryos originated from deviant morphology and/or kinetic cleavage patterns. This case series suggests that some blastocysts derived from embryos with poor conventional morphological score and/or suboptimal morphokinetics can be successfully transferred and might result in live births. Such results might raise awareness that discarding embryos based only on early events is not a suitable approach to give patients the chance to conceive. In conclusion, to date only the transfer of viable embryos after culturing them until day 5 guarantees optimal embryo selection and helps to prevent embryo wastage.
    Full-text · Article · Apr 2014 · Reproductive biomedicine online
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    • "Time-lapse technology offers the possibility of observing the entire progression of embryo development, overcoming the limitations of the traditional periodical observations. In fact, morphokinetics has recently been proposed as an additional selection tool due to its strong relationship with other morphological parameters, and several studies support its link with in-vitro and in-vivo embryo viability (Chamayou et al., 2013; Ciray et al., 2006; Cruz et al., 2011, 2012; Hesters et al., 2008; Lemmen et al., 2008; Lundin et al., 2001; Meseguer et al., 2011a; Mio and Maeda, 2008; Pribenszky et al., 2010; Sakkas et al., 1998; Shoukir et al., 1997; Wong et al., 2010) and even with the ploidy of embryos more recently (Campbell et al., 2012, 2013; Chavez et al., 2012). Fertilization includes the extrusion of the second polar body (PB), the appearance and fading of the pronuclei (PN) or the PN syngamy, events that frequently happen before or after the conventional first embryo observation performed at 16–22 h post insemination, frequently remaining unidentified when the assessment is performed at fixed time points. "
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    ABSTRACT: The morphology of fertilization events has been related to successful implantation by subjective criteria (pronuclei score, pronuclei symmetry and position). This work first described these events by time-lapse technology and then compared the timings of fertilization events (second polar body extrusion, first and second pronuclei appearance, abuttal and fading) in implanted versus nonimplanted embryos in a 2-year cohort retrospective study. A total of 1448 transferred embryos from 842 patients undergoing intracytoplasmic sperm injection with oocyte donation were monitored, 212 embryos from treatments where the number of gestational sacs matched the number of transferred embryos and 687 embryos from treatments no biochemical pregnancy was achieved. The timings at which second polar body extrusion (3.3–10.6 h), pronuclear fading (22.2–25.9 h) and length of S-phase (5.7–13.8 h) occurred were linked successfully to embryo implantation. The other parameters were apparently not related, as determined by image acquisition and time-lapse analysis.
    Full-text · Article · Apr 2014 · Reproductive biomedicine online
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    • "Table 5 in Hesters et al. (2008) "
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    ABSTRACT: Time-lapse observation presents an opportunity for optimizing embryo selection based on morphological grading as well as providing novel kinetic parameters, which may further improve accurate selection of viable embryos. The objective of this retrospective study was to identify the morphokinetic parameters specific to embryos that were capable of implanting. In order to compare a large number of embryos, with minimal variation in culture conditions, we have used an automatic embryo monitoring system. Using a tri-gas IVF incubator with a built-in camera designed to automatically acquire images at defined time points, we have simultaneously monitored up to 72 individual embryos without removing the embryos from the controlled environment. Images were acquired every 15 min in five different focal planes for at least 64 h for each embryo. We have monitored the development of transferred embryos from 285 couples undergoing their first ICSI cycle. The total number of transferred embryos was 522, of which 247 either failed to implant or fully implanted, with full implantation meaning that all transferred embryos in a treatment implanted. A detailed retrospective analysis of cleavage times, blastomere size and multinucleation was made for the 247 transferred embryos with either failed or full implantation. We found that several parameters were significantly correlated with subsequent implantation (e.g. time of first and subsequent cleavages as well as the time between cleavages). The most predictive parameters were: (i) time of division to 5 cells, t5 (48.8-56.6 h after ICSI); (ii) time between division to 3 cells and subsequent division to 4 cells, s2 (≤ 0.76 h) and (iii) duration of cell cycle two, i.e. time between division to 2 cells and division to 3 cells, cc2 (≤ 11.9 h). We also observed aberrant behavior such as multinucleation at the 4 cell stage, uneven blastomere size at the 2 cell stage and abrupt cell division to three or more cells, which appeared to largely preclude implantation. The image acquisition and time-lapse analysis system makes it possible to determine exact timing of embryo cleavages in a clinical setting. We propose a multivariable model based on our findings to classify embryos according to their probability of implantation. The efficacy of this classification will be evaluated in a prospective randomized study that ultimately will determine if implantation rates can be improved by time-lapse analysis.
    Full-text · Article · Aug 2011 · Human Reproduction
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