title: Adherence compounds in embryo transfer media for assisted reproductive technologies.
abstract: BACKGROUND
  This is an update of a Cochrane review first published in The Cochrane Library (2010, Issue 7).To increase the success rate of assisted reproductive technologies (ART), adherence compounds such as hyaluronic acid (HA) and fibrin sealant have been introduced into subfertility management. Adherence compounds are added to the embryo transfer medium to increase the likelihood of embryo implantation, with the potential for higher clinical pregnancy and live birth rates.
  
  
  OBJECTIVE
  To determine whether embryo transfer media containing adherence compounds improved live birth and pregnancy rates in ART cycles.
  
  
  METHODS
  The Menstrual Disorders and Subfertility Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE, EMBASE and PsycINFO electronic databases were searched (up to 13 November 2013) to look for publications that described randomised controlled trials on the addition of adherence compounds to embryo transfer media. Furthermore, reference lists of all obtained studies were checked, and conference abstracts were handsearched.
  
  
  METHODS
  Only truly randomised controlled trials comparing embryo transfer media containing functional (e.g. 0.5 mg/ml HA) concentrations of adherence compounds versus transfer media containing low or no concentrations of adherence compounds were included. The adherence compounds that were identified for evaluation were HA and fibrin sealant.
  
  
  METHODS
  Two review authors selected trials for inclusion according to the above criteria, after which two review authors independently extracted the data for subsequent analysis. Statistical analysis was performed in accordance with the guidelines developed by The Cochrane Collaboration.
  
  
  RESULTS
  Seventeen studies with a total of 3898 participants were analysed. One studied fibrin sealant, and the other 16 studied HA. No evidence was found of a treatment effect of fibrin sealant as an adherence compound. For HA, evidence of a positive treatment effect was identified in the six trials that reported live birth rates (odds ratio (OR) 1.41, 95% confidence interval (CI) 1.17 to 1.69; six RCTs, N = 1950, I(2) = 0%, moderate-quality evidence). Furthermore, the 14 trials reporting clinical pregnancy rates showed evidence of treatment benefit when embryos were transferred in media containing functional concentrations of HA (OR 1.39, 95% CI 1.21 to 1.60; 14 RCTs, N = 3452, I(2) = 46%, moderate-quality evidence) as compared with low or no use of HA. The multiple pregnancy rate (OR 1.86, 95% CI 1.49 to 2.31; five RCTs, N = 1951, I(2) = 0%, moderate-quality evidence) was significantly increased in the high HA group, but no significant differences in adverse event rates were found (OR 0.74, 95% CI 0.49 to 1.12; four RCTs, N = 1525, I(2) = 0%, moderate-quality evidence).
  
  
  CONCLUSIONS
  Evidence suggests improved clinical pregnancy and live birth rates with the use of functional concentrations of HA as an adherence compound in ART cycles. However, the evidence obtained is of moderate quality. The increase in multiple pregnancy rate may be the result of use of a combination of an adherence compound and a policy of transferring more than one embryo. Further studies of adherence compounds with single embryo transfer need to be undertaken.
authors.affiliation: Centre for Reproductive Medicine, Department of Obstetrics and Gynaecology, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands.
authors.forename: Stephan
authors.initials: S
authors.lastname: Bontekoe
authors.forename: Maas Jan
authors.initials: MJ
authors.lastname: Heineman
authors.forename: Neil
authors.initials: N
authors.lastname: Johnson
authors.forename: Debbie
authors.initials: D
authors.lastname: Blake
mesh_terms: D003470:Culture Media / Q000737:chemistry*; D010064:Embryo Implantation / Q000187:drug effects* / Q000502:physiology; D005260:Female; D015718:Fibrin Tissue Adhesive / Q000494:pharmacology*; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology*; D050498:Live Birth; D011247:Pregnancy; D011272:Pregnancy, Multiple; D016032:Randomized Controlled Trials as Topic; D027724:Reproductive Techniques, Assisted; D014014:Tissue Adhesives / Q000494:pharmacology*
chemical_list: D003470:Culture Media; D015718:Fibrin Tissue Adhesive; D014014:Tissue Adhesives; D006820:Hyaluronic Acid