Principal findings from a multicenter trial investigating the safety of follicular-fluid meiosis-activating sterol for in vitro maturation of human cumulus-enclosed oocytes.
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.
Smitz
Johan
J
Center for Reproductive Medicine, Academisch Ziekenhuis, Vrije Universiteit Brussel, Brussels, Belgium.
Picton
Helen-Mary
HM
Platteau
Peter
P
Rutherford
Anthony
A
Cortvrindt
Rita
R
Clyde
Julie
J
Nogueira
Daniela
D
Devroey
Paul
P
Lyby
Karsten
K
Gröndahl
Christian
C
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
D002782:Cholestenes; C100324:4,4-dimethylcholesta-8,14,24-trienol; D005640:Follicle Stimulating Hormone