title: Time-lapse systems for embryo incubation and assessment in assisted reproduction.
abstract: BACKGROUND
  Embryo incubation and assessment is a vital step in assisted reproductive technology (ART). Traditionally, embryo assessment has been achieved by removing embryos from a conventional incubator daily for assessment of quality by an embryologist, under a light microscope. Over recent years time-lapse systems (TLSs) have been developed which can take digital images of embryos at frequent time intervals. This allows embryologists, with or without the assistance of computer algorithms, to assess the quality of the embryos without physically removing them from the incubator.The potential advantages of a TLS include the ability to maintain a stable culture environment, therefore limiting the exposure of embryos to changes in gas composition, temperature and movement. Additionally a TLS has the potential advantage of improving embryo selection for ART treatment by utilising additional information gained through monitoring embryo development.
  
  
  OBJECTIVE
  To determine the effect of a TLS compared to conventional embryo incubation and assessment on clinical outcomes in couples undergoing ART.
  
  
  METHODS
  A comprehensive search of all the major electronic databases, including grey literature, was undertaken in co-ordination with the Trials Search Co-ordinator of the Cochrane Menstrual Disorders and Subfertility Group in July 2014 and repeated in November 2014 to confirm that the review is up to date.
  
  
  METHODS
  Two authors (SA and NA) independently scanned the titles and abstracts of the articles retrieved by the search. Full texts of potentially eligible randomised controlled trials (RCTs) were obtained and examined independently by the authors for their suitability according to the review inclusion criteria. In the case of doubt between the two authors, a third author (LC) was consulted to gain consensus. The selection process is documented with a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow chart.
  
  
  METHODS
  Data were obtained and extracted by two authors. Disagreement was resolved by consensus. Trial authors were contacted by e-mail to obtain further study information and data. All extracted data were dichotomous outcomes and odds ratios (OR) were calculated on an intention-to-treat basis. Where enough data were available, meta-analysis was undertaken.
  
  
  RESULTS
  Three studies involving 994 women were found for inclusion. Data from all three studies were used to address comparison one, TLS with or without cell-tracking algorithms versus conventional incubation. No studies were found to address comparison two, TLS utilising cell-tracking algorithms versus TLS not utilising cell-tracking algorithms.There was only one study which reported live birth (n = 76). The results demonstrated no conclusive evidence of a difference in live birth rate per couple randomly assigned to the TLS and conventional incubation arms of the study (OR 1.1, 95% CI 0.45 to 2.73, 1 RCT, n = 76, moderate quality evidence).All three studies reported miscarriage (n = 994). There was no conclusive evidence of a difference in miscarriage rates per couple randomly assigned to the TLS and conventional incubation arms (OR 0.70, 95% CI 0.47 to 1.04, 3 RCTs, n = 994, I(2) = 0%, low quality evidence).Only one study reported stillbirth rates (n = 76). There were equal numbers of stillbirths in both the TLS and conventional incubation arms of the study. Therefore, there was no evidence of a difference in the stillbirth rate per couple randomly assigned to TLS and conventional incubation (OR 1.0, 95% CI 0.13 to 7.49, 1 RCT, moderate quality evidence).All three studies reported clinical pregnancy rates (n = 994). There was no conclusive evidence of a difference in clinical pregnancy rate per couple randomly assigned to the TLS and conventional incubation arms (OR 1.23, 95% CI 0.96 to 1.59, 3 RCTs, n = 994, I(2) = 0%, low quality evidence). None of the included studies reported cumulative clinical pregnancy rates.
  
  
  CONCLUSIONS
  There is insufficient evidence of differences in live birth, miscarriage, stillbirth or clinical pregnancy to choose between TLS and conventional incubation. Further data explicitly comparing the incubation environment, the algorithm for embryo selection, or both, are required before recommendations for a change of routine practice can be justified.
authors.affiliation: Department of Obstetrics and Gynaecology, University of Auckland, Park Rd, Grafton, Auckland, New Zealand. s.armstrong@auckland.ac.nz.
authors.forename: Sarah
authors.initials: S
authors.lastname: Armstrong
authors.forename: Nicola
authors.initials: N
authors.lastname: Arroll
authors.forename: Lynsey M
authors.initials: LM
authors.lastname: Cree
authors.forename: Vanessa
authors.initials: V
authors.lastname: Jordan
authors.forename: Cindy
authors.initials: C
authors.lastname: Farquhar
mesh_terms: D046149:Embryo Culture Techniques; D047108:Embryonic Development / Q000502:physiology*; D005260:Female; D006801:Humans; D050498:Live Birth; D011247:Pregnancy; D018873:Pregnancy Rate; D016032:Randomized Controlled Trials as Topic; D027724:Reproductive Techniques, Assisted; D059008:Time-Lapse Imaging / Q000379:methods*