A randomized, double-blind, controlled trial of the effect of adding follicular fluid meiosis activating sterol in an ethanol formulation to donated human cumulus-enclosed oocytes before fertilization

Objective:
To evaluate the effect of follicular fluid meiosis activating sterol (FF-MAS) in a 0.2% ethanol formulation on chromosomal status and development of preembryos.

Design:
Multicenter, prospective, randomized, double-blind, five parallel group, controlled trial.

Setting:
Public and private IVF-clinics in Denmark and Sweden.

Patient(s):
Two hundred ten women undergoing IVF treatment donated 310 oocytes.

Intervention(s):
FSH/hCG primed cumulus-enclosed oocytes randomized to 4 hours exposure of medium with 0.1, 1, or 10 μM FF-MAS dissolved in 0.2% ethanol, medium with ethanol 0.2%, or medium with water for injection (control) before insemination.

Main outcome measure(s):
Primary: incidence of human preembryos with chromosomal abnormalities. Secondary: fertilization rate, cleavage rate, and preembryo quality after 68 hours of culture.

Result(s):
At the preembryo level, no significant differences in chromosomal abnormality rate were found among any of the groups. At the blastomere level, a significant increased abnormality rate was observed in the ethanol group and the combined FF-MAS groups compared with the control group. No significant differences in fertilization rate, cleavage rate, or preembryo quality were observed among any of the groups and the control group except for a significant reduction in the number of embryos with ≥2 cells at 26 hours in the ethanol group.

Conclusion(s):
No negative effect of FF-MAS was observed. However, addition of ethanol 0.2% to standard IVF-medium with or without FF-MAS for culturing cumulus-enclosed oocytes for 4 hours before insemination increased the chromosomal abnormality rate at the blastomere level. Further studies of FF-MAS in a nonethanol formulation are under way.