CommentaryEmbryo aneuploidy and the role of morphological and genetic screening
Section snippets
Introduction: chromosome abnormalities, embryos and screening
Data from numerous studies using a wide variety of techniques have demonstrated beyond doubt that a high proportion of human oocytes are affected by chromosome abnormalities. The phenomenon is closely associated with female age. For a woman over 40 years old undergoing IVF treatment, it is typical for more than half of the oocytes retrieved to be chromosomally abnormal (Fragouli et al., 2006, Fragouli et al., 2010a, Kuliev et al., 2003, Pellestor et al., 2003, Sandalinas et al., 2002). Embryos
Biological perspectives
A number of previous studies have looked at the relationship between morphology and aneuploidy. Most investigations have confirmed that a link exists, but have found that correlations are weak and likely to be of little assistance in the selection of euploid embryos for transfer (Alfarawati et al., 2010, Eaton et al., 2009, Hardarson et al., 2003, Magli et al., 2007, Moayeri et al., 2008, Munné et al., 2007, Staessen and Van Steirteghem, 1998). To date, most studies have focused on embryos at
Clinical potential
Whatever the underlying biological cause, there does appear to be a link between aneuploidy and abnormal morphology at the cleavage and blastocyst stages. The clinical question is: can morphological analysis assist the identification of euploid embryos for uterine transfer? In the study by Finn et al., the probability of selecting a chromosomally normal embryo at random was 0.26. Whereas if transfer had been restricted to those embryos achieving the morphological appearance most closely
The efficacy of preimplantation genetic screening
As well as reporting morphological data, Finn and colleagues have also provided a summary of their experience using preimplantation genetic screening (PGS), assessing the copy number of nine chromosomes using FISH in order to assist the transfer of euploid embryos in poor-prognosis patients. Although many laboratories have now moved to comprehensive chromosome analysis methods (e.g. CGH, microarray-CGH and single-nucelotide polymorphism array), a better understanding of the potential benefits
Acknowledgements
Dagan Wells is funded by NIHR Biomedical Research Centre Programme.
References (29)
- et al.
Removal of two cells from cleavage stage embryos is likely to reduce the efficacy of chromosomal tests employed to enhance implantation rates
Fertil. Steril.
(2007) - et al.
Increased efficiency of preimplantation genetic diagnosis for infertility using ‘no result rescue’
Fertil. Steril.
(2007) - et al.
Assessment of day-3 morphology and euploidy for individual chromosomes in embryos that develop to the blastocyst stage
Fertil. Steril.
(2009) - et al.
Chromosomal abnormalities in a series of 6, 733 human oocytes in preimplantation diagnosis for age-related aneuploidies
Reprod. Biomed. Online
(2003) - et al.
Embryo morphology and development are dependent on the chromosome complement
Fertil. Steril.
(2007) - et al.
Day-3 embryo morphology predicts euploidy among older subjects
Fertil. Steril.
(2008) - et al.
Improved implantation after preimplantation genetic diagnosis of aneuploidy
Reprod. Biomed. Online
(2003) - et al.
Maternal age, morphology, development and chromosome abnormalities in over 6000 cleavage-stage embryos
Reprod. Biomed. Online
(2007) - Alfarawati, S., Fragouli, E., Colls, P., et al., 2010. The relationship between blastocyst morphology, chromosomal...
- et al.
Fluorescence in-situ hybridization analysis of two blastomeres from day-3 frozen-thawed embryos followed by analysis of the remaining embryo on day-5
Hum. Reprod.
(2004)
Human gene expression first occurs between the four- and eight-cell stages of preimplantation development
Nature
Discordance among blastomeres renders preimplantation genetic diagnosis for aneuploidy ineffective
J. Assist. Reprod. Genet.
Impact of cleavage-stage embryo biopsy in view of PGD on human blastocyst implantation: a prospective cohort of single embryo transfers
Hum. Reprod.
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Evaluation of artificial intelligence using time-lapse images of IVF embryos to predict live birth
2021, Reproductive BioMedicine OnlineCitation Excerpt :Scoring systems for the morphological evaluation of embryos have been developed to increase birth rates (Dennis et al., 2006; Goto et al., 2011; Van den Abbeel et al., 2013; Luke et al., 2014). However, these methods are insufficient to predict a live birth because there is no clear correlation between morphology and chromosomal aneuploidy (Wells, 2010; Alfarawati et al., 2011). Chromosomal aneuploidy of the embryo increases with a woman's age (Grande et al., 2012; Franasiak et al., 2014) resulting in decreased live birth rates due to lack of implantation and increased miscarriage rates.
Validation of a next-generation sequencing–based protocol for 24-chromosome aneuploidy screening of blastocysts
2016, Fertility and SterilityCitation Excerpt :However, polar body biopsy only reflects the chromosome status from the maternal contribution and cannot guarantee a normal karyotype in the implanted embryos. Cleavage-stage biopsy reflects both the paternal and maternal contribution of the embryos, but the chromosomal aneuploidy rate can be as high as 30% to 85% (18, 19), bringing difficulties for implantation. Our previous study also showed only 26.09% of cleavage embryos were euploid (10).
Impact of blastocyst biopsy and comprehensive chromosome screening technology on preimplantation genetic screening: A systematic review of randomized controlled trials
2015, Reproductive BioMedicine OnlineCitation Excerpt :To improve IVF clinical outcomes, preimplantation genetic screening (PGS) has been proposed to infertile couples seeking assisted reproduction technique treatments (Brezina et al., 2013; Gianaroli et al., 1999; Moutou et al., 2014; Munne et al., 1993; Rubio, 2013). The process of PGS consists of selecting the most competent (euploid) embryos for transfer, through aneuploidy screening after embryo biopsy (Fragouli and Wells, 2012; Kaser and Ginsburg, 2014; Munne, 2002; Wells, 2010). Indications for PGS use in IVF include advanced maternal age (Gianaroli et al., 1999; Hanson et al., 2009; Kuliev and Verlinsky, 2003; Milan et al., 2010; Munne et al., 1995, 1998; Orris et al., 2010; Platteau et al., 2005; Rubio et al., 2013a; Schoolcraft et al., 2009), repeated implantation failure (Blockeel et al., 2008; Greco et al., 2014; Rubio et al., 2013a), recurrent spontaneous abortion (Munne et al., 2005; Shahine and Lathi, 2014) and severe male factor infertility (Harper and Sengupta, 2012; Rodrigo et al., 2014).
Choosing the best embryo by time lapse versus standard morphology
2015, Fertility and SterilityCitation Excerpt :It is generally accepted that aneuploid embryos are less likely to implant or usually result in early pregnancy loss (42, 43). Although traditional morphological evaluation has limited success at identifying aneuploid embryos (15, 44–46), several observational studies have proposed time-lapse parameters as predictive of aneuploidy with diverging conclusion. Chavez et al. (2012) (47) evaluated the parameters previously identified by Wong et al. (39) and Conaghan et al. (23) to predict formation of blastocyst and usable blastocyst.
Invited commentary: The politics of human embryo research and the motivation to achieve PGD
2011, Reproductive BioMedicine OnlineDetermination of fetal chromosome aberrations from fetal DNA in maternal blood: Has the challenge finally been met?
2011, Expert Reviews in Molecular Medicine