The Endometrial Receptivity Array or ERA has been around for 10 years. When the first
research about ERA was published in 2011, there was great excitement among fertility specialists
that it could be a game changer for improving IVF pregnancy rates. Now, its 2021, the ERA
is performed in every fertility center around the world. There have been dozens of studies
and publications about the ERA. Has it lived up to the expectations? Stay tuned
First, a little background. In order for a pregnancy to occur, you need essentially
two things. A healthy viable embryo and a receptive uterine lining or endometrium.
For many years now, we have had the ability to grow embryos to the blastocyst stage
and the ability to identify embryos with the correct number of chromosomes. With this
enhanced ability to identify the best embryos, attention was shifted to the uterine lining.
In order for an embryo to implant, the uterine lining must be prepared using
two hormones. Estrogen, which makes the uterine lining thicker,
and progesterone which transforms the lining to make it receptive to an embryo. The length of
time that estrogen is needed to thicken the lining does not seem to be very important.
Pregnancy rates are not affected. The length of time for progesterone however, is very important.
The changes that occur in the uterine lining do not happen immediately, they take several days.
The time during which the embryo is able to attach is known as the window of implantation or WOI.
Placing an embryo into the uterus either before
or after the window of implantation will result in a lower chance for pregnancy.But
so many questions remain. When is -the optimal time? Is it the same every month? How long does
that implantation window remain open? Is the timing the same for all women?
It is known that the cells of the uterine lining have genes that produce many different
kinds of proteins. The activity of these genes changes with different hormones and with time.
In 2011, researchers identified 134 genes whose activity helped them predict pregnancies
in a small group of patients. It seemed that by looking at which genes were active or inactive,
that they could accurately define the window of implantation. In other words, with the help
of some fancy computers algorithms, you could take a sample of cells from the uterine lining,
look at which genes were active in those cells and determine whether the lining
was ready to have an embryo implant, or whether it was too early or too late.
Based on limited data from the early days of IVF, most IVF programs would transfer a blastocyst on
the 6th day from the start of progesterone. It was thought that this was fixed and the same
for all women at all times. As data from the ERA began to emerge, however, it seemed that
while most women followed this rule, some did not. It appeared as though there were some women
who might see a higher chance for pregnancy with an earlier transfer or a later transfer.
A number of early studies suggested that this was a valuable test for couples
frozen embryo transfers, especially those with multiple failed implantations or who
were very overweight. As time went on, the quality of the studies being done improved.
In 2020, a large multi center study compared three groups: couples undergoing a fresh transfer,
a frozen transfer or a frozen transfer after an ERA. Three quarters of the couples were
undergoing their first embryo transfer, in other words, this was not a study about
recurrent implantation failure. This study was able to demonstrate a slight benefit in the ERA
group only after couples had gone through multiple transfers over the course of a year.
Another study compared couples who had failed to become pregnant after at least
three embryo transfers. They determined that couples who used tested embryos had higher a
higher pregnancy rate but that couples who had an ERA did not better than those who didn’t
Recently, researchers from Boston published the results of a new study on ERA. They looked
at 133 patients who had an ERA performed and had an embryo transfer based on those results
and closely matched them to 353 non-ERA patients. They found no difference in the pregnancy rate,
miscarriage rate or live birth rate between those who had the ERA and those who did not. Then they
compared the patients who had an abnormal result on the ERA, which is called non receptive. These
are patients in whom the timing of the transfer was changed to a presumably more optimal time.
Compared to couples who did not do the ERA, they found no difference in the pregnancy rate.When
they looked at couples who had multiple failed embryo transfers they still found no difference.
Our InfertilityTV Bottom line is this. After 10 years, the ERA test is certainly not the
game changer we were hoping for. Although it is premature to state that the ERA is
completely useless, more work needs to be done to determine which couples, if any, may benefit
from having this test. In the meantime, it is certainly reasonable for couples to undergo
multiple embryo transfers without having this particular test.