What can be the causes of failed implantation in egg donation cycles?
Implantation failure is a constant source of worry – it’s a very common issue, and it can be caused by a large list of reasons – in fact, we hosted not one, but several #IVFWebinars on the topic. You can find the latest one here.
In theory, egg donation bypasses many of the possible causes of implantation failure. This, however, does not mean it’s a guaranteed method of achieving pregnancy; while it definitely improves implantation rates, some causes of implantation failure aren’t related to oocytes. What, then, can cause a failure in an egg donation cycle? We selected three experts to help us understand this very complex topic.
Our experts are:
- Dr. Esther Marban, Clinica Tambre, Spain
- Dr. Harry Karpouzis, Pelargos IVF, Greece
- Dr. Natalia Szlarb, IVF Spain, Spain
Answer from Dr. Marban
First of all, we have to think about the embryo. We know that a chromosomally healthy embryo will have a higher implantation rate so maybe in that kind of patient we will have an embryo that does not implant because of this. It’s true that egg donation patients won’t have a very high number of embryos with those kinds of problems but if we transfer an embryo that is not chromosomally healthy, the embryo is not going to implant. So, we can analyse the embryo to make sure that the embryo is healthy in that way.
Apart from that, it’s important that the patient should be in the best possible condition. We can apply some tests, like the Clotinab immunological test, to check if the patient is healthy in that way. If we find a problem, we have the chance of introducing some treatment to avoid problems with implantation failure. Regarding the uterus, the place where we will put the embryo, it’s very important to have it in the best condition as possible. We can analyse the uterus with ultrasound and if we find a problem such as a polyp or fibroid, we can remove it so that it won’t have any negative effect.
In recent years, ER activity tests have been applied to make sure that the egg is implanted at the best moment of the patient’s cycle. We know that some patients can have the window of implantation—that is, the moment when the embryo will be implanted—in a higher percentage. A small group of patients might have a window of implantation not in the must-come moment. So, we can do a test like this and if it turns out that the endometrium isn’t receptive, we can make the transfer at the right moment for the patient.
Answer from Dr. Karpouzis
The reasons for implantation problems in egg donation can be related to the embryos and the quality of the eggs themselves or to the chromosomes—for example, abnormalities of the embryos, which can be usually related to the sperm or sometimes to the egg if the selection of the donor was not appropriate. It can be related to the environment of the womb, the uterus, or immunological reasons and in the end, it can also be because of infection. We have discovered that there is no 100% accurate test that can really indicate chlamydia, ureaplasma or mycoplasma. So, sometimes the environment of the uterus inside the lining of the womb can be infected by several factors that can affect the chances of success of a transfer. In cases of recurrent implantation failure with egg donation, we usually advise a course of treatment with antibiotics a long time before the embryo transfer and we have found that if we treat such indications with 20 days of antibiotics beforehand, we see some improvement because often endometritis—infection of the womb lining—can play an important role. Sometimes the implantation window can be moved.
We have discovered that the best time to transfer an embryo is on day 5, but on some occasions—for example, if we do an ERA test, which is used to determine the implantation window—at this time the endometrium could be pre-receptive or post-receptive. This is a very good test that tells us whether next time we should make the transfer a little earlier or later after more or fewer days of progesterone pretreatment. Finally, we need to look at the lining of the womb. On many occasions, we have found problems within the womb lining like polyps, diaphragms, adhesions. A hysteroscopy is required to identify the reason and prescribe treatment and this can affect the chances of an egg donation cycle succeeding. Hydrosalpinx can sometimes be hidden. For example, we can only find them if we do HSG (hysterosalpingogram). On occasions like this, a laparoscopy or removal of the salpinx does play a role. The immunological factors can be related to many other issues and intralipid or steroid treatment, or other procedures depending on the specific case, can increase the chances of success. Even the herpes virus has been found to have a negative impact. In cases of recurrent failures, we sometimes give a herpes pretreatment before we do the transfer and we have found improvement on this as well.
Finally, there occasions when the lining of the womb does not grow. We know that we have not found any reason for this but the lining of the womb does not exceed 7 mm. The GCSF, which is a growth factor, a medication that can increase the blood flow in the endometrium has been used on occasions like this and we do have better results. In general, it needs very thorough testing for all the factors and we need to make sure that none of these issues are present before we go ahead with other options.
Answer from Dr. Szlarb
In answer to the second question regarding the reasons for implantation failure in egg donation cycles, when we review egg donation cycles, we always have to focus on 3 main implantation areas. The first is the quality of the donor eggs. We have to be aware that even though the donors are young, not all the embryos which they generate are euploid—genetically normal—and that the euploidy rate is 60–80% in egg donation cycles. So, when we have complicated cases, we recommend performing Preimplantation Genetic Screening to define genetically normal euploid embryos.
The second reason why we can experience implantation failure in egg donation cycles is the receptivity window. We see that some patients, even though they implant the embryos and have positive pregnancy tests, still have their implantation window moved. Usually, 70% of all the patients need 5 days of progesterone to open the implantation window. In patients with recurrent implantation failure, we see that the implantation window is moved, that some of them need 6–8 days of progesterone to be receptive. That’s why in patients with recurrent implantation failure in egg donation, if the first or second transfer failed, definitely the uterus lining biopsy with ER Map is the method of choice to determine what’s going on with the lining.
The third problem that we can experience in egg donation cycles is immunology. This involves the number of natural killer cells, which could be elevated. We recommend performing a biopsy for natural killer cells and define the uterine natural killer cells in the womb, not in the blood (not circulating natural killer cells), and in selected cases—especially when we match the second or third donor—we focus on HLA. We have to be aware that embryos show to the mum HLA-C so in selected cases we match donors to our patients according to their HLA.