title: Correlation between standard blastocyst morphology, euploidy and implantation: an observational study in two centers involving 956 screened blastocysts.
abstract: OBJECTIVE
  Does conventional blastocyst morphological evaluation correlate with euploidy (as assessed by comprehensive chromosome screening (CCS) of trophectoderm (TE) biopsies) and implantation potential?
  
  
  CONCLUSIONS
  A moderate relation between blastocyst morphology and CCS data was observed but the ability to implant seems to be mainly determined by the chromosomal complement of preimplantation embryos rather than developmental and morphological parameters conventionally used for blastocyst evaluation.
  
  
  BACKGROUND
  Combined with improving methods for cryopreservation and blastocyst culture, TE biopsy and CCS is considered to be a promising approach to select euploid embryos for transfer. Understanding the role of morphology in blastocyst stage preimplantation genetic screening (PGS) cycles may help in further optimizing the cycle management and clinical outcomes.
  
  
  METHODS
  This is a multicenter retrospective observational study performed between January 2009 and August 2013. The study includes the data analysis of 956 blastocysts with conclusive CCS results obtained from 213 patients following 223 PGS cycles. Single frozen embryo transfer (FET) cycles of 215 euploid blastocysts were performed where it was possible to track the implantation outcome of each embryo transferred.
  
  
  METHODS
  PGS was offered to infertile patients of advanced maternal age (>35 years) and/or with a history of unsuccessful IVF treatments (more than two failed IVF cycles) and/or previous spontaneous abortion (more than two spontaneous miscarriages). Prior to TE biopsy for CCS, blastocyst morphology was assessed and categorized in four groups (excellent, good, average and poor quality). The developmental rate of each embryo reaching the expanded blastocyst stage was defined according to the day of biopsy post-fertilization. Day 5 and Day 6 biopsied blastocysts were defined as faster and slower growing embryos, respectively. A novel blastocyst biopsy method, not requiring the opening of the zona pellucida at the cleavage stage of embryo development, was used. Linear regression models were used to test the relationship between blastocyst morphology and developmental rate CCS data and FET cycle outcomes of euploid blastocysts.
  
  
  RESULTS
  Among the embryological variables assessed (morphology and developmental rate), only blastocyst morphology was predictive of the CCS data. The euploidy rate was 56.4, 39.1, 42.8 and 25.5% in the excellent, good, average and poor blastocyst morphology groups, respectively. A diagnosis of complex aneuploidy was also associated with blastocyst morphology (P < 0.01) with 6.8, 15.2, 17.4 and 27.5% of excellent, good, average and poor quality embryos, respectively, showing multiple chromosome errors. Faster and slower growing embryos showed a similar aneuploidy rate. Regression logistic analysis showed that none of the parameters used for conventional blastocyst evaluation (morphology and developmental rate) was predictive of the implantation potential of euploid embryos. The implantation potential of euploid embryos was the same, despite different morphologies and developmental rates.
  
  
  CONCLUSIONS
  The study is limited by its retrospective nature. A higher sample size or a prospective randomized design could be used in future studies to corroborate the current findings.
  
  
  CONCLUSIONS
  This study provides knowledge for a better laboratory and clinical management of blastocyst stage PGS cycles suggesting that the commonly used parameters of blastocyst evaluation are not good enough indicators to improve the selection among euploid embryos. Accordingly, all poor morphology and slower growing expanded blastocysts should be biopsied and similarly considered for FET cycles. This knowledge will be of critical importance to achieve similar cumulative live birth rates in PGS programs compared with conventional IVF, avoiding the potential for exclusion of low quality but viable embryos from the biopsy and transfer procedures. Future research to identify non-invasive biomarkers of reproductive potential may further enhance selection among euploid blastocysts.
  
  
  BACKGROUND
  No funding was obtained for the study. All authors have no conflicts to declare.
  
  
  BACKGROUND
  None.
authors.affiliation: GENERA, Center for Reproductive Medicine, Clinica Valle Giulia, Via G. De Notaris 2b, 00197 Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Capalbo
authors.forename: Laura
authors.initials: L
authors.lastname: Rienzi
authors.forename: Danilo
authors.initials: D
authors.lastname: Cimadomo
authors.forename: Roberta
authors.initials: R
authors.lastname: Maggiulli
authors.forename: Thomas
authors.initials: T
authors.lastname: Elliott
authors.forename: Graham
authors.initials: G
authors.lastname: Wright
authors.forename: Zsolt Peter
authors.initials: ZP
authors.lastname: Nagy
authors.forename: Filippo Maria
authors.initials: FM
authors.lastname: Ubaldi
mesh_terms: D000328:Adult; D000782:Aneuploidy; D001755:Blastocyst; D010064:Embryo Implantation / Q000502:physiology*; D004624:Embryo Transfer / Q000379:methods; D047108:Embryonic Development / Q000502:physiology*; D005260:Female; D006801:Humans; D007246:Infertility / Q000628:therapy; D011247:Pregnancy; D012189:Retrospective Studies
keywords: aneuploidies; blastocyst biopsy; blastocyst morphology; embryo evaluation; preimplantation genetic screening