title: Obstetrical and perinatal outcomes following blastocyst transfer compared to cleavage transfer: a systematic review and meta-analysis.
abstract: Is blastocyst transfer safe when compared to cleavage stage embryo transfer regarding obstetric and perinatal outcomes?
  
  
  
  The clinical equipoise between blastocyst and cleavage stage embryo transfer remains as the evidence associating blastocyst transfer with some adverse perinatal outcomes is of low/very low quality.
  
  
  
  Extended embryo culture to the blastocyst stage provides some theoretical advantages and disadvantages. While it permits embryo self-selection, it also exposes those embryos to possible harm due to the in vitro environment. Both effectiveness and safety should be weighed to permit evidence-based decisions in clinical practice.
  
  
  
  This is a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies reporting perinatal outcomes for singletons comparing the deliveries resulting from blastocyst and cleavage stage embryo transfer. Observational studies were included because the primary outcomes, perinatal mortality and birth defects, are rare and require a large number of participants (>50 000) to be properly assessed. The last electronic searches were last run on 11 March 2016.
  
  
  
  There were 12 observational studies encompassing 195 325 singleton pregnancies included in the study. No RCT reported the studied outcomes. The quality of the included studies was evaluated according to the Newcastle-Ottawa Scale and the quality of the evidence was evaluated according to GRADE criteria.
  
  
  
  Blastocyst stage transfer was associated with increased risks of preterm birth (<37 weeks), very preterm birth (<32 weeks), large for gestational age and perinatal mortality, although the latter was only identified from one study. Conversely, blastocyst stage transfer was associated with a decrease in the risks of small for gestational age and vanishing twins, although the latter was reported by only one study.
  
  
  
  The observational nature of the included studies and some inconsistency and imprecision in the analysis contributed to decreasing our confidence in the estimates.
  
  
  
  Due to the overall low quality of available evidence, the clinical equipoise between cleavage stage and blastocyst transfer remains. More large well-conducted studies are needed to clarify the potential risks and benefits of blastocyst transfer. As this review was initiated to support global recommendations on best practice, and in light of the challenges in lower resource settings to offer extended culture to blastocyst stage, it is critical to take into consideration these obstetric and neonatal outcomes in order to ensure any recommendation will not result in the overburdening of existing maternal and child health care systems and services.
  
  
  
  No external funding was either sought or obtained for this study. The authors have no competing interests to declare.
  
  
  
  CRD42015023910.
authors.affiliation: Department of Obstetrics and Gynecology, Ribeirao Preto Medical School, University of Sao Paulo, Av. Bandeirantes, 3900 - Monte Alegre, Ribeirao Preto - SP, 14049-900, Brazil.
authors.forename: W P
authors.initials: WP
authors.lastname: Martins
authors.affiliation: SMEAR fertilidade, Reproductive Medicine, Av. Aurea Aparecida Bragheto Machado, 220 - City Ribeirao, Ribeirao Preto - SP, 14021-570, Brazil.
authors.forename: C O
authors.initials: CO
authors.lastname: Nastri
authors.affiliation: GENERA Centre for Reproductive Medicine, Clinica Valle Giulia, via de Notaris 2b, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Rienzi
authors.affiliation: HRP (UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction), Avenue Appia 20, 1211 Geneva, Switzerland (at the time of the study); Population Council, Reproductive Health Programme, Center for Biomedical Research, 1230 York Ave, New York, NY 10065, USA.
authors.forename: S Z
authors.initials: SZ
authors.lastname: van der Poel
authors.affiliation: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Pennsylvania, 3701 Market Street, Suite 800, Philadelphia, PA 19104, USA.
authors.forename: C R
authors.initials: CR
authors.lastname: Gracia
authors.affiliation: Division of Reproductive Medicine, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
authors.forename: C
authors.initials: C
authors.lastname: Racowsky
mesh_terms: D001755:Blastocyst; D002970:Cleavage Stage, Ovum / Q000637:transplantation*; D004624:Embryo Transfer / Q000379:methods*; D005260:Female; D006801:Humans; D050498:Live Birth; D011247:Pregnancy; D011256:Pregnancy Outcome; D018873:Pregnancy Rate
keywords: assisted reproduction / embryo culture / human / blastocyst / obstetrical / perinatal