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Fertilization and mouse embryo development in the presence of midazolam
1Department of Biological Sciences, Old Dominion University, Norfolk, VA 23529-0266.
Abstract:
Mouse embryo in vitro development elucidates the effect of a pharmacologic agent on cellular differentiation. Midazolam provides conscious sedation for patients undergoing egg retrieval for in vitro fertilization and is found in patient follicular fluid. Mouse preimplantation embryo formation and development were evaluated in the presence of midazolam. Midazolam was cocultured with two-cell mouse preimplantation embryos over 72 h and injected systemically just before ovulation and coitus. Concentrations to 12.5 micrograms/mL displayed no significant toxic effects on in vitro two-cell-to-blastocyst development. Doses to 35.0 mg/kg did not prevent or impair in vivo fertilization. Midazolam has no adverse effect on in vitro development of two-cell-to-blastocyst-stage embryos nor on in vivo fertilization and cell division at concentrations approximating and exceeding those that ova are exposed to during clinical anesthesia. Midazolam is recommended for use to induce sedation in human in vitro fertilization where association with gametes and zygotes is probable.
Insights
Midazolam, used for conscious sedation during egg retrieval, shows no adverse effects on mouse embryo development or fertilization. This finding supports its safety for human in vitro fertilization procedures.
Area of Science:
- Reproductive biology
- Developmental toxicology
- Pharmacology
Background:
- Midazolam is a sedative used in procedures like egg retrieval for in vitro fertilization (IVF).
- The drug has been detected in follicular fluid, indicating potential exposure to gametes and early embryos.
- Understanding its effects on early embryonic development is crucial for patient safety in assisted reproductive technologies.
Purpose of the Study:
- To evaluate the impact of midazolam on mouse preimplantation embryo development in vitro.
- To assess the effects of midazolam on in vivo fertilization and early cell division.
- To determine the safety of midazolam for gametes and zygotes during IVF procedures.
Main Methods:
- Mouse two-cell embryos were cultured in vitro with midazolam (up to 12.5 µg/mL) for 72 hours.
- Midazolam was administered systemically to female mice before ovulation and coitus to assess in vivo fertilization.
- Embryo development and fertilization rates were monitored.
Main Results:
- Midazolam up to 12.5 µg/mL did not significantly affect in vitro development from the two-cell to blastocyst stage.
- Systemic midazolam doses up to 35.0 mg/kg did not impair in vivo fertilization.
- No adverse effects were observed on embryo development or fertilization at concentrations relevant to clinical anesthesia.
Conclusions:
- Midazolam demonstrates no adverse effects on the in vitro development of mouse embryos to the blastocyst stage.
- The drug does not negatively impact in vivo fertilization or early cell division in mice.
- Midazolam is recommended for conscious sedation in human IVF, given its safety profile concerning gametes and zygotes.