title: The non-independence of treatment outcomes from repeat IVF cycles: estimates and consequences.
abstract: BACKGROUND
  It is generally acknowledged that the outcomes of IVF treatments are correlated between repeat cycles in the same couple and that these effects need to be allowed for in the analysis of such treatments. However, there are few studies that have attempted to estimate the magnitude of these effects or their clinical consequences.
  
  
  METHODS
  We use the embryo-uterus model, extended to include inter-cycle correlations in both the embryo and uterine components to estimate these effects in a large data set of 12 480 embryo transfer cycles from 8768 UK IVF patients, including embryo grading parameters. Empirical Bayes estimates are used to predict the consequences of previous cycle failures on the prognosis of future cycles.
  
  
  RESULTS
  Statistically and clinically significant correlations can be detected which amount to a median odds ratio of 2.3 (95% CI: 1.8-2.9) in the chances of an embryo being viable between any two randomly selected patients. These act predominantly through the embryo component of the model. Inclusion of these effects in the embryo model does alter the estimates and predictions, but not dramatically. Around 10 cycle failures are required to reduce the probability of success in future cycles to half that of the initial cycle.
  
  
  CONCLUSIONS
  There are important inter-cycle correlations between embryos transferred across different cycles from the same patients, implying substantial unmeasured prognostic embryo characteristics. The implications for extended culture and cryopreserved embryos need further investigation as well as similar consideration of the other components of treatment, particularly response to stimulation. Although these effects should not be ignored they have limited impact in the development of predictive models for individual cycles, but do need to be accounted for when considering multiple cycle treatment programmes. For individual patients the failure of one or several embryo transfers does not have a big impact on the chances of success in future cycles. The magnitude of the correlations suggests that for any individual couple, previous cycle implantation failures do not imply a greatly reduced prognosis for future cycles.
authors.affiliation: Health Sciences-Methodology, Manchester Academic Health Science Centre (MAHSC), University of Manchester, Manchester M13 9WL, UK. steve.roberts@manchester.ac.uk
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Roberts
authors.forename: Christos
authors.initials: C
authors.lastname: Stylianou
mesh_terms: D000328:Adult; D001499:Bayes Theorem; D057286:Electronic Health Records; D010064:Embryo Implantation; D004624:Embryo Transfer; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D007246:Infertility / Q000175:diagnosis / Q000628:therapy*; D050498:Live Birth; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011247:Pregnancy; D011256:Pregnancy Outcome; D059285:Pregnancy, Twin; D011379:Prognosis; D012372:ROC Curve; D020554:Sperm Injections, Intracytoplasmic; D006113:United Kingdom; D055815:Young Adult