title: Blastocyst vs cleavage-stage embryo transfer: systematic review and meta-analysis of reproductive outcomes.
abstract: OBJECTIVE
  Blastocyst transfer in assisted reproduction techniques could be advantageous because the timing of exposure of the embryo to the uterine environment is more analogous to a natural cycle and permits embryo self-selection after activation of the embryonic genome on day 3. Conversely, the in-vitro environment is likely to be inferior to that in vivo, and in-vitro culture beyond embryonic genomic activation could potentially harm the embryo. Our objective was to identify, appraise and summarize the available evidence comparing the effectiveness of blastocyst vs cleavage-stage embryo transfer.
  
  
  METHODS
  This was a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the transfer of blastocysts (days 5-6) with the transfer of cleavage-stage embryos (days 2-3) in women undergoing in-vitro fertilization or intracytoplasmic sperm injection. The last electronic searches were run on 1 August 2016. Abstracts and studies with a mean difference between the two study groups of > 0.5 for the number of embryos transferred were excluded.
  
  
  RESULTS
  We screened 1187 records and assessed 33 potentially eligible studies. Twelve studies were included, comprising a total of 1200 women undergoing blastocyst transfer and 1218 undergoing cleavage-stage embryo transfer. We observed low-quality evidence of no significant difference of blastocyst transfer on live birth/ongoing pregnancy (relative risk (RR), 1.11 (95% CI, 0.92-1.35), 10 RCTs, 1940 women, I2= 54%), clinical pregnancy (RR, 1.10 (95% CI, 0.93-1.31), 12 RCTs, 2418 women, I2= 64%), cumulative pregnancy (RR, 0.89 (95% CI, 0.67-1.16), four RCTs, 524 women, I2= 63%) and miscarriage (RR, 1.08 (95% CI, 0.74-1.56), 10 RCTs, 763 pregnancies, I2= 0%). There was moderate-quality evidence of a decrease in the number of women with surplus embryos after the blastocyst-stage embryo transfer (RR, 0.78 (95% CI, 0.66-0.91)). Overall, the quality of the evidence was limited by the quality of the included studies and by unexplained inconsistency across studies.
  
  
  CONCLUSIONS
  Current evidence shows no superiority of blastocyst compared with cleavage-stage embryo transfer in clinical practice. As the quality of the evidence for the primary outcomes is low, additional well-designed RCTs are still needed before robust conclusions can be drawn. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
authors.affiliation: SEMEAR Fertilidade, Reproductive Medicine, Ribeirão Preto, Brazil.|Department of Obstetrics and Gynecology, Ribeirão Preto Medical School, University of Sao Paulo, Ribeirão Preto, Brazil.
authors.forename: W P
authors.identifier: http://orcid.org/0000-0002-7593-5607
authors.initials: WP
authors.lastname: Martins
authors.affiliation: SEMEAR Fertilidade, Reproductive Medicine, Ribeirão Preto, Brazil.
authors.forename: C O
authors.initials: CO
authors.lastname: Nastri
authors.affiliation: GENERA Centre for Reproductive Medicine, Clinica Valle Giulia, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Rienzi
authors.affiliation: HRP (the UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction), Geneva, Switzerland.|Population Council, Reproductive Health Program, New York, NY, USA.
authors.forename: S Z
authors.initials: SZ
authors.lastname: van der Poel
authors.affiliation: Division of Reproductive Endocrinology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Gracia
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Racowsky
mesh_terms: D001755:Blastocyst; D002970:Cleavage Stage, Ovum / Q000637:transplantation*; D004624:Embryo Transfer; D005260:Female; D006801:Humans; D011247:Pregnancy; D011256:Pregnancy Outcome; D018873:Pregnancy Rate; D011272:Pregnancy, Multiple
keywords: ICSI; IVF; assisted reproduction; blastocyst; embryo culture techniques; embryo transfer; evidence-based medicine; in-vitro fertilization