Modeling of airborne embryonic volatile compounds (VOCs) in the IVF culture environment – their concomitant cytotoxic concentration within the growth media and embryo.

2019  |  Worrilow, K. C., A. R. Urrutia, H. T. Huynh, J. T. Fox.

Fertility and Sterility



VOCs are a common component of laboratory ambient air. VOCs are unique in their polarity, molecular weight and structure and play a critical role in preimplantation toxicology and epigenetic processes. This study sought to define the mechanisms of cytotoxicity associated with VOCs found in the IVF culture environment. The concomitant concentrations of VOCs common to IVF laboratories were modeled with Henry’s Law (HL) from the gaseous to aqueous phase, and the final resulting concentration within the embryo was modeled with octanol water partitioning coefficients (OWPC).


HL was used to model VOC mass transfer from the air to the water/media phase. This model uses the air-water partitioning coefficient and the definition that the ratio between the liquid and air phase concentration is defined and unique for each organic compound. The OWPC was used for each compound to correlate the mass transfer from the water/media phase to the embryo using the ratio between the organic phase and water phase concentration.

Materials and Methods

Evaluation of over 40 IVF laboratories identified the mean total VOC (TVOC) levels and 6 most common VOCs. HL and OWPC calculations determined the concomitant VOC concentrations in the culture media, embryo in culture, and time required to reach equilibrium for each compound. Research has shown that TVOC concentrations greater than or equal to 500 ppb in the media is embryotoxic and exerts a statistically significant impact on blastocyst conversion rates. Air phase VOC concentrations were compared to known embryotoxic VOC levels in cell culture media to determine if typical VOC levels in IVF laboratories are embryotoxic.


The concentration of each VOC within the embryo (Cembryo) was modeled based on airborne VOC levels measured. This modeled Cembryo was compared to the embryotoxic level when embryos were cultured in an aqueous environment of 500 ppb VOCs. Levels of acetone, formaldehyde and isopropanol measured in IVF laboratories resulted in cytotoxic cellular levels.


Airborne VOCs are driven to reach equilibrium and can be magnified in concentration as they partition from the air to the cell culture media, and ultimately, into the embryo. Once cellular, the VOCs exert a negative influence on blastocyst conversion, implantation, and clinical pregnancy rates. This study related the measured concentration of airborne VOCs to the modeled concentration within the embryo. This novel study further defines the mechanisms of cytotoxicity of VOCs by defining their partition from the gaseous to aqueous phase, and most importantly, to the cellular phase. This data furthers our understanding of the role of VOCs in epigenetic variation and cytotoxicity.