Choosing embryos for in vitro fertilization (IVF) is fraught with uncertainty. The process has only a 35 percent success rate, and transferring more than one embryo to increase the odds of successful implantation increases a woman’s chances of having multiple births or requiring a selective abortion.
By analyzing time-lapse videos of fertilized eggs as they develop, a team of researchers from Stanford University School of Medicine has identified three specific milestones that eggs must reach in order to form a blastocyst, a critical stage. The team created an algorithm for monitoring the embryos’ progress, and says this algorithm can predict which will develop to a blastocyst and which will die with 93 percent certainty. The technique could be used to enhance decision-making in the clinic, which currently relies on subjective evaluation of an embryo’s quality.
For reasons unknown, human embryos have a particularly high failure rate, and between half and more than two-thirds of IVF embryos fail to reach the blastocyst stage. Currently, embryos are usually chosen based on their visual appearance, which is checked at specific points in their development. Renee Reijo Pera, from the Institute for Stem Cell Biology and Regenerative Medicine at Stanford, and lead author of the new work, which is published in Nature Biotechnology, says that even though visual cues are used to evaluate embryos in the clinic, there was a paucity of imaging data about the complete course of their progress.
To better understand how embryos look over time, her team studied a set of 242 one-celled embryos that had been frozen 12 to 18 hours after fertilization. Embryos are now usually frozen after they have had a chance to develop for three to five days; thawing and observing embryos while still in the one-celled stage allowed the researchers to track their progress from the earliest stages of development.
The team took time-lapse images of the cells using dark-field microscopy, a technique that is useful for imaging live cells. First author Connie Wong led an analysis of the images to identify visual parameters that corresponded to survival and successful formation of a blastocyst at day five. Out of 10 parameters studied, the researchers found three of them to be critical to success. All of them related to timing: the final stage of cell division, in which the cell physically separates into two; the interval between the first and second cell division cycle; and the interval between the second and third cell division.