title: Principal findings from a multicenter trial investigating the safety of follicular-fluid meiosis-activating sterol for in vitro maturation of human cumulus-enclosed oocytes.
abstract: OBJECTIVE
  To evaluate the safety of applying follicular-fluid meiosis-activating sterol (FF-MAS) in vitro to immature human oocytes.
  
  
  METHODS
  Phase I bicenter, randomized, parallel-group, controlled, partially blinded trial.
  
  
  METHODS
  Third-level referral academic centers, including reproductive biology and genetics laboratories.
  
  
  METHODS
  Endocrinologically normal women with a medical indication for IVF or intracytoplasmic sperm injection, or healthy volunteers.
  
  
  METHODS
  Subjects were randomized at a ratio 1 to 6 into either conventional GnRH-agonist and recombinant FSH stimulation (IVO) for oocyte retrieval, or minimally stimulated in vitro maturation (IVM) with the use of recombinant FSH. Retrieved immature oocyte cumulus complexes were cultured for 30 or 36 hours in one of six IVM culture conditions containing FF-MAS (range, 0.1-20 microM). Polar body-extruded oocytes from the IVO and IVM groups were processed for chromosomal analysis.
  
  
  METHODS
  The primary endpoint was the incidence of metaphase II stage oocytes with numeric chromosomal abnormalities, using full (spectral karyotyping) or partial (fluorescent in situ hybridization with seven probes) karyotyping or Giemsa count. A secondary objective was to document the frequency of metaphase II oocytes after IVM with FF-MAS supplements.
  
  
  RESULTS
  Oocyte cumulus complexes obtained from the IVO (mean, 8.9) and IVM (mean, 6.2) groups had equal maturation rates. Compared to IVO, exposure of germinal-vesicle oocytes for a maturation period of 30 hours did not increase aneuploidy. An exposure period of 36 hours doubled the aneuploidy rate, but this was significant only for the 20-muM dose of FF-MAS.
  
  
  CONCLUSIONS
  Inclusion of 1-10 microM FF-MAS in a 30-hour IVM protocol is safe.
authors.affiliation: Center for Reproductive Medicine, Academisch Ziekenhuis, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Smitz
authors.forename: Helen-Mary
authors.initials: HM
authors.lastname: Picton
authors.forename: Peter
authors.initials: P
authors.lastname: Platteau
authors.forename: Anthony
authors.initials: A
authors.lastname: Rutherford
authors.forename: Rita
authors.initials: R
authors.lastname: Cortvrindt
authors.forename: Julie
authors.initials: J
authors.lastname: Clyde
authors.forename: Daniela
authors.initials: D
authors.lastname: Nogueira
authors.forename: Paul
authors.initials: P
authors.lastname: Devroey
authors.forename: Karsten
authors.initials: K
authors.lastname: Lyby
authors.forename: Christian
authors.initials: C
authors.lastname: Gröndahl
mesh_terms: D000328:Adult; D000782:Aneuploidy; D002782:Cholestenes / Q000009:adverse effects*; D002869:Chromosome Aberrations; D005260:Female; D005307:Fertilization in Vitro; D005640:Follicle Stimulating Hormone; D006801:Humans; D066298:In Vitro Techniques; D008540:Meiosis; D009865:Oocytes / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D020554:Sperm Injections, Intracytoplasmic
chemical_list: D002782:Cholestenes; C100324:4,4-dimethylcholesta-8,14,24-trienol; D005640:Follicle Stimulating Hormone