How Long Can Frozen Embryos Last?
We learned this week that a woman gave birth using a 24-year-old embryo.
Tannis Toohey/Toronto Star via Getty Images; photo of Emma Gibson courtesy of National Embryo Donation Center
A 26-year-old woman made headlines this week for giving birth to baby from a donated embryo that was frozen 24 years ago. Tina Gibson gave birth to daughter Emma on November 25 after getting pregnant through in vitro fertilization (IVF). Tina’s husband Benjamin has cystic fibrosis, which can cause infertility.
Emma’s birth may constitute a record for longest frozen human embryo to result in birth—the embryo donation center says it’s an all-time record—but there’s actually no way to know for sure since the “ages” of donated embryos are not logged in any official database. A 2011 paper noted that a woman gave birth following IVF with a donated embryo that had been frozen for 19 years and 7 months, so this case at least beats that one.
But this story does beg the question: how long, in theory, can human embryos be cryopreserved and still be viable? Well, we don’t know yet, admits Catherine Racowsky, director of the Brigham and Women's Hospital IVF Laboratory and vice president of the American Society for Reproductive Medicine. “But if they are stored at the correct temperature (-196 degrees Celsius), it’s likely a very long time.”
Back in the 80s, researchers proved that cryopreserved mouse embryos could survive a simulated 2,000 years and then go on to be born healthy. As for human embryos (aka fertilized eggs), a 2013 study found that the duration of storage had no effect on the pregnancy and birth rate.
Embryos are frozen by using cryoprotectant solutions that essentially act as “anti-freeze” to replace the water in the cells so that no ice crystals can form. (Such crystals could puncture and damage the cells.) The embryos are then placed in storage tanks of liquid nitrogen at -196 degrees C, where they must remain fully immersed in order to remain frozen.
This temperature is close to absolute zero, or the temperature where we think no biological processes occur. So in theory, cryopreservation is truly hitting the “pause” button on the development of life. (And we’re talking about very early life: The most developmentally advanced human embryos that can be cryopreserved are 120-cell blastocysts, which are embryos about 5 to 6 days after fertilization, too young to even implant in the uterus.) Thawing out that embryo and placing it in a human uterus is like hitting the “play” button; it should be as if no time has passed.
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There are two methods of freezing. The older method, slow freezing, involves adding small amounts of cryoprotectant to the tissue over the course of 10 to 20 minutes. It takes one to two hours for the embryo to reach the optimum temperature. The embryo used in this recent birth after 24 years on ice was frozen using this older method. The newer technique, vitrification, cools tissue 10,000 times faster by using higher concentrations of cryoprotectants. Vitrification has only been used for embryo storage in the last decade or so, and research comparing how different freezing methods might impact storage-length potential is scant. One recent analysis showed slightly improved cyro-survival rates with vitrification compared to slow freezing.
“In our experience, once the embryos or eggs are frozen the passage of time likely does not matter as long as the conditions in the storage tank are maintained,” says Vitaly Kushnir, a reproductive endocrinologist at the Center for Human Reproduction in New York. “The technique of freezing and thawing is more important.” Kushnir says slow freezing uses an automated system to lower the temperature gradually as cryoprotectants are added; vitrification is a manual process but because it’s very fast, it helps avoid the formation of damaging ice crystals. “There are advantages and disadvantages to each technique, but currently vitrification is favored by many fertility centers for freezing embryos and eggs while slow freezing is favored for freezing ovarian tissue samples.”
Racowsky says each step in both the freezing or thawing procedures has to be performed correctly to avoid the potential for embryo loss or damage. “We are dealing with cells that are exquisitely sensitive,” she says.
On embryologist says that, based on what we know now, human eggs and embryos can probably be stored indefinitely, but there are some storage issues that need to be addressed. “Scientists and engineers need to develop ways for embryologists to store eggs and embryos safely, identify samples, perform inventory and transport samples without disrupting temperature,” writes Jacque Cohen, an embryologist and lab director of The ART Institute of Washington at Walter Reed National Military Medical Center, on fertilityiq.com. “When this goal is achieved, spending an eternity in liquid nitrogen and coming out of it unscathed would not be a far-fetched idea.”
The Gibsons told CNN they have two more embryos from the anonymous donor, so if they choose to have more kids via IVF, they could make headlines again.
Use of frozen embryos is far from revolutionary: the US first baby to be born from a cryopreserved embryo was way back in 1986. According to the Centers for Disease Control and Prevention, the use of donated embryos is not common but it nearly doubled between 2006 and 2015, with the number of these IVF cycles rising from 866 to 1,700. That still makes the procedure significantly less popular than using a donated egg: In 2015, roughly 20,000 IVF cycles were performed in the US using donor eggs.
When it comes to live birth rates, donated frozen embryos appear to be slightly less successful than using a donated egg combined with her partner’s sperm or sperm from a donor. In 2015, only 39 percent of frozen donor embryo transfers resulted in live births, compared to 56 percent of transfers involving never-frozen embryos from a donor egg and 43 percent for frozen embryos using a donor egg. The group that facilitated the recent donation says its 2014 birth rate from donated frozen embryos was 54 percent.
Kushnir’s research has shown lower birth rates using frozen eggs compared to fresh eggs. He says that while it’s possible “[egg] quality may be negatively affected by cryopreservation and thawing,” he cautions that the data these findings are based on “did not allow adjustments for confounding patient characteristics, such as donor and recipient ages, infertility diagnosis, and embryo stage.”
And while these procedures are generally considered as safe as traditional IVF with fresh eggs or embryos, the use of any donor materials has been found to increase the risk of complications for both the pregnant person and fetus. Use of donated egg and sperm are both separately linked to an increased risk of preeclampsia, which is a case of extremely high blood pressure that, if left untreated, can be fatal. Last year, an analysis of 11 cohort studies reported a three-fold increase in the chances developing preeclampsia in donor egg/embryo pregnancies, compared to IVF pregnancies that used the patient’s own eggs. The risks were not attributable to multiple pregnancies or the patient’s age.
Studies have also shown that use of donor eggs or embryos is associated with an increased risk of pregnancy-induced hypertension, preterm delivery, and low birth weight. A recent study found that when compared to use of only a donor egg, “double donation”—use of donated embryo or of a donor egg and donor sperm—was also linked to an increased risk of gestational diabetes.
Kushnir says the increase in risk of complications can often be attributed to the health of patients who turn to egg or embryo donation. “It has to do with the advanced age of recipients of donor eggs and embryos which raises risk for adverse pregnancy outcomes,” he says. “There may also be more immune rejection of a pregnancy arising from donor gametes than the patient’s own gametes.”
A recent review article analyzed the results of 35 studies on the topic of pregnancy outcomes with the use of donor eggs, also known as oocytes. The studies compared the outcomes of pregnancies achieved with donor eggs or embryos with those achieved either through traditional IVF or by spontaneous conception (that is, couples who get pregnant via intercourse after having a child using reproductive technology). The researchers found that for preeclampsia, there was an increased risk of two-fold in singletons and three-fold for twins in egg donations. For preterm birth, there was an increased risk in both singletons and twins. The researchers believe that egg donation should be listed in professional guidelines as a known risk factor for preeclampsia, and that single-embryo transfers should be the golden standard in oocyte donation since multiple pregnancies always add to the risk of complications.