title: Artificial oocyte activation with calcium ionophore does not cause a widespread increase in chromosome segregation errors in the second meiotic division of the oocyte.
abstract: OBJECTIVE
  To study the effect of artificial oocyte activation (AOA) on chromosome segregation errors in the meiotic divisions.
  
  
  METHODS
  Prospective cohort study with historical control.
  
  
  METHODS
  Private/academic IVF centers.
  
  
  METHODS
  Fifty-six metaphase II oocytes were donated from 12 patients who had undergone IVF between June 2008 and May 2009.
  
  
  METHODS
  Oocytes were activated by 40 minutes' exposure to 100 μM calcium-ionophore. The activated oocyte was tubed and analyzed by array comparative genomic hybridization and/or single-nucleotide polymorphism genotyping and maternal haplotyping (meiomapping). A control sample of embryos derived from normally fertilized oocytes was included for comparison.
  
  
  METHODS
  Incidence of chromosome segregation errors in artificially activated and normally fertilized oocytes in relation to pronuclear evaluation.
  
  
  RESULTS
  Of 49 oocytes that survived the warming procedure, thirty-nine (79.6%) activated. Most activated normally, resulting in extrusion of the second polar body and formation of a single or no pronucleus (2PB1PN: 30 of 39, 76.9%; or 2PB0PN: 5 of 39, 12.8%). Twenty-seven of these were analyzed, and 16 (59.3%) were euploid, showing no effect of AOA on meiotic segregation. Single-nucleotide polymorphism analysis of normally activated oocytes confirmed normal segregation of maternal chromosomes. No difference in the proportion of meiosis II type errors was observed between artificially activated oocytes (28.6%; 95% confidence interval 3.7%-71.0%) compared with embryos obtained from normally fertilized oocytes (44.4%; 95% confidence interval 13.7%-78.8%). The abnormally activated oocytes, with ≥2PN (4 of 39, 10.3%) were diploid, indicating a failure to coordinate telophase of meiosis II with polar body extrusion.
  
  
  CONCLUSIONS
  From this preliminary dataset, there is no evidence that AOA causes a widespread increase in chromosome segregation errors in meiosis II. However, we recommend that it be applied selectively to patients with specific indications.
authors.affiliation: GENERA, Centers for Reproductive Medicine, Rome, Italy; GENETYX, Marostica, Italy. Electronic address: capalbo@generaroma.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Capalbo
authors.affiliation: The Bridge Centre, London, United Kingdom; School of Biosciences, University of Kent, Canterbury, United Kingdom.
authors.forename: Christian S
authors.initials: CS
authors.lastname: Ottolini
authors.affiliation: School of Biosciences, University of Kent, Canterbury, United Kingdom.
authors.forename: Darren K
authors.initials: DK
authors.lastname: Griffin
authors.affiliation: GENERA, Centers for Reproductive Medicine, Rome, Italy; GENETYX, Marostica, Italy.
authors.forename: Filippo Maria
authors.initials: FM
authors.lastname: Ubaldi
authors.affiliation: The Bridge Centre, London, United Kingdom; School of Biosciences, University of Kent, Canterbury, United Kingdom; Illumina, Cambridge, United Kingdom.
authors.forename: Alan H
authors.initials: AH
authors.lastname: Handyside
authors.affiliation: GENERA, Centers for Reproductive Medicine, Rome, Italy; GENETYX, Marostica, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Rienzi
mesh_terms: D000328:Adult; D061207:Calcium Ionophores / Q000494:pharmacology* / Q000633:toxicity; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000139:chemically induced; D020090:Chromosome Segregation / Q000187:drug effects*; D055028:Comparative Genomic Hybridization; D005260:Female; D005298:Fertility / Q000187:drug effects; D005300:Fertility Agents, Female / Q000494:pharmacology* / Q000633:toxicity; D005307:Fertilization in Vitro; D006239:Haplotypes; D006801:Humans; D059471:In Vitro Oocyte Maturation Techniques; D007246:Infertility / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D008540:Meiosis / Q000187:drug effects*; D009865:Oocytes / Q000187:drug effects* / Q000378:metabolism; D011003:Ploidies; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D018570:Risk Assessment; D013997:Time Factors; D017211:Treatment Failure
chemical_list: D061207:Calcium Ionophores; D005300:Fertility Agents, Female
keywords: Calcium ionophore; chromosome segregation; fertilization failure; meiosis; oocyte activation