Kevin Loewke, a postdoctoral fellow now at Auxogyn in Menlo Park, California, developed a method of automatically measuring the three parameters using an image-analysis algorithm. Loewke says that the challenge in tracking the progress of the cells is converting two-dimensional microscopic images into information about the three-dimensional structure of the embryo, especially as multiple cells can block one another from view. His solution was to create a predictive model of each cell of the embryo and use the model to determine the timing of each milestone. The algorithm has been licensed by Auxogen, which plans to develop a product that would use the approach to determine embryo viability.
All of the parameters discovered by the team occurred before day two of the embryo’s development. Many clinics grow the embryo until it reaches the blastocyst stage at day five, but some scientists believe that spending too long in culture might raise the risk of altered gene expression in the infant. “The advantage is, if you can predict blastocyst formation by day two, you can get it out of the artificial environment sooner,” says Marcelle Cedars, director of the Division of Reproductive Endocrinology and Infertility at the University of California, San Francisco , who was not involved in the study.
But Cedars says that, “even in the youngest patients, 50 percent of embryos that make it to the blastocyst stage won’t implant.” The question is whether predicting the development into a blastocyst will also predict successful implantation. “It’s halfway there, but it’s not telling you if this is going to make a baby,” she says. Other methods of screening embryos include genetically analyzing a biopsy, or measuring molecular factors in the culture medium that surrounds the embryos. Cedars says that none of these have so far proven successful at boosting pregnancy rates.
As part of their study, the Stanford researchers also analyzed gene expression in the cells at different stages of embryonic development. The parameters they discovered all occurred at a time when the embryos had not yet activated their own genes, and were relying on genetic instruction from the egg. Cedars says this finding reinforces the idea that “the biggest driver of having a good embyro is the egg.”
The scientists also discovered that at these early stages of development, the cells in the embryo are acting autonomously, expressing genes at different times. This lack of coordination could help explain why some embryos fare so poorly.