Earlier today we noted that Robert Edwards won a 2010 Nobel Prize for his work developing in vitro fertilization. But more than three decades after Edwards’ work came to fruition with the first IVF child’s birth, the technique is still somewhat haphazard—two-thirds of the time, it doesn’t lead to a live birth. Now, with a new approach to watching the first day or two of an embryo’s existence, scientists may be able to take a leap forward in both their understanding of a life’s first moments and in the success rate of IVF.
In a study published in Nature Biotechnology, Connie Wong and colleagues watched nearly 250 embryos develop over six days. They made the videos like the one seen above using time-lapse photography at the microscopic level, which showed the key differences between successful and failed embryos.
Successful embryos had an initial cytokinesis, or division of the cell’s cytoplasm, lasting between 0 and 33 minutes, a gap between first and second cell divisions lasting 7.8 – 14.3 hours, and an interval between second and third cell divisions of 0 – 5.8 hours. The pattern was so uniform that it was possible to automate the analytical process, using a computer algorithm to predict whether embryos would go on to develop successfully. [Nature]
That algorithm was impressive: 93 percent of the time, the scientists could correctly predict whether an embryo would develop normally. (In the video, the top embryo is developing along the successful pattern; the bottom one is not.)
The reason this could be so important for IVF is timing. Doctors are in a dilemma: When they perform IVF, they want to hold off on implantation until embryos are several days old and reach the blastocyst stage. At that stage it’s easier to tell which will be successful. But more and more studies suggest it’s risky to leave the embryos outside of the body for too long.
A lab dish is hardly the same as the nurturing environment of the uterus, and the longer these embryos are allowed to grow outside of the body, the more they may diverge from normal development. While studies are still ongoing, data so far suggest that IVF embryos are more vulnerable to developmental abnormalities during these early stages of development in the dish, which may explain their high death rate. “We’d like to bypass having all of these things happening in the dish,” she says, “and transfer embryos at day two [after fertilization].” [TIME]
Furthermore, the success rate of present procedures is only about one-third. That leads fertility clinicians to embed multiple embryos hoping one of them will succeed. Occasionally this results in rare but highly-publicized cases of multiple births, like the octuplets born to “Octomom” Nadya Suleman last year.
If this new method of monitoring the growth of embryos could be developed on a wide scale, doctors could get around that problem. Perhaps they could identify embryos on the path to success and implant them after just two days, reducing that risky exposure to the outside world. And if doctors were more confident about embryos’ success, they could get around the Octomom problem.
For study coauthor Renee Reijo Pera, the results are more than just a means to improve IVF. Her movies show something more basic about how we developed in our first moments.
For the first time, she says, it’s clear that the every cell in the very early embryo is acting independently of the others, and that the fate of the embryo as a whole depends on how synchronous the cells are in their developmental cycle. All of this is occurring well before the embryo’s own gene are turned on, when the egg is still directed development, so Reijo Pera suspects that much of the survival of days-old embryos depends on the genes passed down from the mother. How this early template affects the activity of the embryo’s genes, once they come into play, is another question that the movies may reveal. [TIME]
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Video: Wong et. al.