title: Comparative intrauterine development and placental function of ART concepti: implications for human reproductive medicine and animal breeding.
abstract: BACKGROUND
  The number of children conceived using assisted reproductive technologies (ART) has reached >5 million worldwide and continues to increase. Although the great majority of ART children are healthy, many reports suggest a forthcoming risk of metabolic complications, which is further supported by the Developmental Origins of Health and Disease hypothesis of suboptimal embryo/fetal conditions predisposing adult cardiometabolic pathologies. Accumulating evidence suggests that fetal and placental growth kinetics are important features predicting post-natal health, but the relationship between ART and intrauterine growth has not been systematically reviewed.
  
  
  METHODS
  Relevant studies describing fetoplacental intrauterine phenotypes of concepti generated by in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) and somatic cell nuclear transfer (SCNT) in the mouse, bovine and human were comprehensively researched using PubMed and Google Scholar. Intrauterine growth plots were created from tabular formatted data available in selected reports.
  
  
  RESULTS
  ART pregnancies display minor but noticeable alterations in fetal and placental growth curves across mammalian species. In all species, there is evidence of fetal growth restriction in the earlier stages of pregnancy, followed by significant increases in placental size and accelerated fetal growth toward the end of gestation. However, there is a species-specific effect of ART on birthweights, that additionally vary in a culture condition-, strain-, and/or stage at transfer-specific manner. We discuss the potential mechanisms that underlie these changes, and how they are affected by specific components of ART procedures.
  
  
  CONCLUSIONS
  ART may promote measurable alterations to intrauterine growth trajectory and placental function. Key findings include evidence that birthweight is not a reliable marker of fetal stress, and that increases in embryo manipulation result in more deviant fetal growth curves. Because growth kinetics in early life are particularly relevant to adult metabolic physiology, we advise more rigorous assessment of fetal growth and placental function in human ART pregnancies, as well as continued follow-up of ART offspring throughout post-natal life. Finally, strategies to minimize embryo manipulations should be adopted whenever possible.
authors.affiliation: Laboratory of Molecular Endocrinology, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Enrrico
authors.initials: E
authors.lastname: Bloise
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Sky K
authors.initials: SK
authors.lastname: Feuer
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, CA, USA rinaudop@obgyn.ucsf.edu.
authors.forename: Paolo F
authors.initials: PF
authors.lastname: Rinaudo
mesh_terms: D000022:Abortion, Spontaneous / Q000453:epidemiology; D000818:Animals; D001724:Birth Weight; D001947:Breeding; D005260:Female; D005307:Fertilization in Vitro; D005313:Fetal Death / Q000209:etiology; D047109:Fetal Development; D051272:Glucose Transporter Type 1 / Q000502:physiology; D051274:Glucose Transporter Type 3 / Q000502:physiology; D023421:Models, Animal; D010920:Placenta / Q000502:physiology; D011247:Pregnancy; D018456:Reproductive Medicine; D027724:Reproductive Techniques, Assisted / Q000009:adverse effects; D020554:Sperm Injections, Intracytoplasmic
chemical_list: D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3
keywords: Developmental Origins of Health and Disease; IVF; assisted reproductive technology; fetal and placental growth