The IVF process is fairly straightforward—but just like humans, it continues to evolve as new research is done on how to give parents the best possible chance of having a baby. Some of this research has involved the transfer of the embryo into the uterus, and whether that should occur three or five days after the eggs and sperm are combined in the lab. Prior to any transfer, however, the eggs and sperm are collected. “We put them together in the laboratory, either by just putting the sperm around the eggs in a petri dish, or injecting sperm directly into the egg, depending on how good the sperm are,” explains Ruben Alvero, MD, professor of obstetrics and gynecology at Stanford Medical School and division director of reproductive endocrinology and infertility at the Lucile Packard Children’s Hospital. “The next day, we figure out if the egg is fertilized or not. At that point, the embryo…is kept in an incubator and cultured.” The length of time for which it is cultured, however, depends on a few different factors. Ahead, find out what differentiates between a three or five-day transfer, and why an endocrinologist might prefer one or the other.
What Is a Day 3 Transfer?
During the 1990s and 2000s, a three-day embryo transfer was the norm, says Joshua Klein, MD, a reproductive endocrinologist, and chief clinical officer at Extend Fertility. “In the earliest days of IVF…no one knew that we could support the growth of a human embryo in the laboratory,” he explains. “At first, [doctors] would actually do a one day transfer. But as lab technology and understanding improved, they realized that we could reliably support the growth of the embryo for additional [time], until day three.” The advantage is that the embryos have extra time to develop before transferring into the uterus. “When we allow [the embryos] to grow for a little bit longer, many of them will show their true colors,” says Dr. Klein. “It’s essentially a selection tool to have a better idea of which embryos are the most likely…to create a pregnancy.”
What Is a Day 5 Transfer?
Just as doctors and researchers experimented with culturing embryos in the lab for three days, they decided in the early 2010s to push it out to five days so they could monitor the embryos for a little bit longer before transferring to the uterus. “By the early to mid-2010s, a lot of the labs were routinely culturing to day five,” notes Dr. Klein. The extra time gives the embryos a chance to grow even longer and prove themselves viable for transfer.
Choosing a Day 3 Embryo Transfer
While three-day transfers are relatively rare these days, there are a few circumstances that would lead a reproductive endocrinologist to recommend one. “This patient may be older, let’s say over the age of 40, or they may have a history of having poor outcomes with previous IVF cycles,” notes Dr. Alvero. “Maybe we know that their sperm quality or egg quality is not very good. Or their pre-stimulation testing tells us that they’re not going to be good responders.” In these cases, a day three transfer may be recommended to give the highest possible chance of pregnancy. Even though less is known about the embryos prior to a day three transfer, they offer patients in these categories the best chance of implantation. “Oftentimes, you get to day five and there are no embryos to transfer. That’s a very difficult emotional situation,” Dr. Alvero says. “So from that perspective, it’s worthwhile to give the patient the satisfaction of having an embryo transfer. Then, at least, there’s the hope of a pregnancy.”
Choosing a Day 5 Embryo Transfer
The main reason most clinics use a day five transfer today is that around day five, the embryo enters a new developmental stage called a blastocyst, meaning it has made it past its first major developmental milestone. “This essentially allows us to put in fewer embryos of better quality, with a higher confidence that they’ll potentially create a pregnancy,” says Dr. Klein. A day five transfer, or a blastocyst-stage transfer, may even be done on day six or even day seven, Dr. Klein adds, depending on when the embryo passes this milestone.
What About Frozen Transfers?
Even though day five transfers are now the go-to, frozen transfers are also becoming increasingly popular. “A frozen transfer means you take out the eggs, make them into embryos, wait a few days to let them grow, then freeze whatever you’ve got,” explains Dr. Klein. “Then, in the subsequent month, you take out one of those embryos from the freezer and you return it to the patient’s body on the day that the uterus is receptive.” By the fifth day, the embryo might have 100 to 120 cells, points out Dr. Alvero. “So we can remove a few cells in a microscopic procedure that is very safe for the embryo,” he adds. “From there, tests can be done on those cells to determine if the embryo has any chromosomal abnormalities.” The most common aneuploidy is trisomy, or when there is an extra chromosome. Conditions that result from extra chromosomes include Down syndrome (trisomy 21), Patau syndrome (trisomy 13), and Edwards syndrome (trisomy 18). Other tests can determine if an embryo has genes or conditions for which one or both of the parents may be a carrier. “There are literally hundreds of things we can test for,” adds Dr. Alvero, noting that the main goal in testing is to reduce the chances of a miscarriage. The other reason parents might choose a frozen transfer is that waiting a month may increase the chances of implantation even further. “There are some studies that suggest that the willingness of the uterine lining to receive the embryo may be decreased during the month in which the egg retrieval was performed,” says Dr. Klein. This is because the patient is given hormone injections to stimulate the production of multiple eggs at once, which artificially increases levels of key hormones that influence how ready the uterus is to receive the embryo. “You may be better off letting all the drugs clear out of your system, and then the following month, putting the embryo into a more normal lining,” Dr. Klein adds.
A Word from Verywell
If using IVF offers you the best chance of having a baby, reproductive endocrinologists will work closely with you to determine the strategy that will maximize those chances. If you are over 40, or testing suggests you might be a poor responder, a day three transfer may be used, while a day five transfer is recommended for patients who are likely to have a positive outcome. Still, some people are opting for frozen transfers if they choose to do genetic testing on their embryos. Regardless, each person is different, and your healthcare provider will help you determine the optimal strategy for you.
