A New Way to Predict IVF Success: Film the Embryo

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With more than four million babies and counting, in vitro fertilization (IVF) is a well-established way for couples who otherwise couldn’t have children to start or expand a family. For some, it’s their only option.

It has been more than three decades since a physician produced the first successful pregnancy through IVF, a process that involves extracting and fertilizing an egg with sperm in a lab dish, creating an embryo and transferring it to a woman’s womb. (That doctor, Robert Edwards, was awarded the Nobel Prize in Physiology and Medicine on Monday for his achievement.) But the success rate for a live birth still remains disappointingly low, on average around 30%. So researchers at Stanford have come up with an innovative way to improve the chances of a pregnancy by selecting only the strongest and healthiest embryos. (More on Time.com: 5 Pregnancy Taboos Explained (or Debunked)).

Led by Dr. Renee Reijo Pera, director of human embryonic stem cell research and education and a professor of obstetrics and gynecology, the group predicted with 93% accuracy which embryos generated during IVF were most likely to lead to a successful pregnancy. The team was able to peek into the very earliest stages of human development, when the embryo divides for the very first time in the two days after fertilization, by making a movie of the process and then measuring differences between those early steps. “What we’ve done is make a movie of the entire pathway and process rather than taking pictures at stagnant times,” she says.

Currently, technicians at IVF clinics play a waiting game with embryos; the longer the embryos are left to grow in the dish, the more confident IVF doctors are that those that survive will result in a viable fetus when transplanted into a woman’s uterus. Most technicians may not even check embryos in the first two days after fertilization, because they prefer to transfer embryos when they are slightly older and more stable, just as they reach something called the blastocyst stage at four or five days old. If the embryo has not arrested and stopped growing by then, then it is likely to continue growing in the womb. (More on Time.com: Building a Brighter Kid: Consider IVF)

But, says Reijo Pera, 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].”

What’s more, the uncertainty has led to the common practice of transferring several embryos at the same time, to ensure that at least one of the embryos results in a baby, but in many cases that can lead to multiple births with all of their complications for both the mother and developing fetuses. In some cases, couples are faced with the difficult decision of having to selectively abort one or more embryos during pregnancy to protect the health of both the mother and child. (More on Time.com: Study: IVF Causes Higher Rates of Baby Boys).

With the new method of scoring embryos almost as soon as they are formed, doctors may be able to transfer embryos earlier, and by reducing these practices, they may perhaps even improve the overall success rate of IVF. The process, says Reijo Pera, does not require any special equipment other than a good microscope hooked up to a special dark field light camera that records the activity of the embryos over a period of eight to 15 hours after fertilization. Each embryo to be tested is placed in a well, and based on three major measurements, a computer program alerts the technician about which embryos fit the desired profile. After hours of filming 100 embryos that had been frozen after IVF and then thawed, the team determined that three factors were the most predictive of robust embryos: 1) the time that the embryos took to complete their first cleavage, splitting into two equal cells in no more than 33 minutes, 2) dividing again anywhere between nearly eight hours and 14 hours later, from two cells into four cells, and 3) then cleaving again from four cells into eight cells within six hours after the last division.

Testing the predictive capabilities of these precise intervals in an IVF setting is the next step, and Reijo Pera has co-founded a company that has received venture capital funding to conduct such a trial. She plans to use the test to predict which embryos are most likely to survive, transplant them into women, and document the outcomes to determine if the selection improved pregnancy rates. (More on Time.com: How the First Nine Months Shape the Rest of Your Life).

While that application alone would make the test remarkable, Reijo Pera, as a developmental biologist, is also excited by the more basic science that her embryo movies revealed. 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. With the first generation of IVF babies reaching the age at which they are having their own children, there is evidence that their unique emergence from a lab dish may have long term effects on everything from their cancer risk to their cognitive abilities.

So such knowledge of the events in the first 24 to 48 hours after fertilization can help to improve not only reproductive success but may some day guide researchers to a better understanding of genetic diseases that may begin as early as in the first few days after fertilization.

More on Time.com:

IVF Pioneer Robert Edwards Wins Nobel Prize

A New Artificial Ovary May Someday Boost Women’s Success with In Vitro

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