Have you suffered a failed IVF or egg donation cycle because of embryos failing to implant? What to do if the embryo does not attach to the uterus? Could anything have been differently in that cycle? Should the doctors try a different approach during your next IVF cycle? These and more questions have been answered during a live webinar with Dr Harry Karpouzis, MD, Scientific Director and Founder of IVF Pelargos Fertility Group.
Dr Karpouzis talked about different approaches to implantation failure which could occur during an IVF treatmen
t or in natural conception. According to statistics, only about 25% of all couples trying to conceive naturally, get pregnant every month. The rest experience what we may call an implantation failure.
Recurrent implantation failures – definition
According to Dr Karpouzis, there are several different definitions of recurrent implantation failures. It is referred to either as 3 failed IVF cycles with good quality embryos or 3 unsuccessful cycles with 2 embryos of at least good quality. Additionally, other sources describe a recurrent implantation failure as a failure of clinical pregnancy after 4 good quality embryos transferred (with at least 3 fresh or frozen cycles) in women under the age of 40. What is important, one needs to make sure not to confuse a recurrent implantation failure with a recurrent pregnancy loss.
Recurrent implantation failures – the risk factor
Dr Karpouzis admits that the major risk factor for recurrent implantation failure
in IVF is maternal age.
It makes things worse in several ways:
- it increases the risk of aneuploidy,
- causes higher endometrial-embryo asynchrony,
- and reduces the oocyte retrieval as well as blastocyst formation,
- additionally, it affects endometrial thickness.
Other important factors that may negatively contribute to recurrent implantation failures are a high BMI, stress, and smoking.
Causes of recurrent implantation failures
All the causes of recurrent implantation failures may be divided into maternal, paternal and embryo factors. When we talk about maternal reasons, we think of anatomic abnormalities (e.g. endometrial septum, fibroids, polyps, adhesions), thrombophilia (disturbed blood flow), immunological issues or non-receptive endometrium. The embryo causes relate mainly to genetic or chromosomal abnormalities that affect the embryo implantation. However, an implantation failure may sometimes occur even if both a mother and the embryo are all right. Then it is generally the matter of the synchronisation between the embryo and the endometrium.
Dr Karpouzis stresses that all of these causes may be dealt with either surgically (like in case of fibroids or polyps) or pharmacologically (as with the use of hormones to increase the endometrium thickness). There are also innovative methods that help to increase the implantation rate, such as PRP (Platelet Rich Plasma)
and GCSF (granulocyte colony stimulating factor) that are proved to have a therapeutic effect on the endometrium. Finally, when all the treatment types fail, surrogacy might be the solution. However, it is a complicated issue as it entails a lot of legal and financial aspects. Interestingly, a lot of clinics today use endometrial scratching as the cure for almost all endometrium-related implantation failures. In Dr. Karpouzis’ opinion, this method is definitely overused. It should be prescribed only when endometrial factor is obvious, and a hysteroscopy is needed as well.
Other factors responsible for implantation failures
Two other important factors responsible for implantation failures after IVF programmes are infections and endometriosis. The former can be treated with the right doses of antibiotics. When it comes to endometriosis, doctors must choose the right protocol for each individual patient. With severe disease, they need to operate before and reduce its impact before they go ahead. Sometimes, when AMH is very poor and there were previous surgeries in a patient’s medical history, they prefer not to operate but to down regulate the AMH level instead. However, Dr Karpouzis stresses that it is important not to down-regulate too much as otherwise the ovaries would not recover as well.
As mentioned before, some risk factors for a recurrent implantation failure might be of embryo origin. An embryo can be affected by both egg quality and sperm quality. In the case of a male factor, it is advisable to do both DNA fragmentation and oxidative stress analysis to investigate the problem properly. Then, if DNA fragmentation is diagnosed, there are fertilisation techniques in the laboratory that can be used, such as PICSI, MACS or IMSI.
Dr Karpouzis says that the quality of eggs
depends on only one factor – a woman’s age. Of course, ovarian reserve, AMH and AFC are all contributing factors. However, as every case is different, doctors have to ensure the best protocol for each female patient in order to choose the proper duration of stimulation as well as the right trigger and its timing. Only in that way they know that the quality of the egg is not affected by the IVF protocol but by the genetic material.
, on the other hand, are not only in women but also in couples who have implantation failures. So, it is highly important to conduct karyotype testing on both a woman and a man to determine a higher rate of mosaicism and chromosome rearrangements such as translocations or inversions. When the chromosomal abnormalities are observed, doctors may do an advanced PGT-SR test to help in identifying aneuploid embryos and – as a result – choose only “the healthy” ones. Definitely, the treatment needs to personalised here, too.
In conclusion, Dr Karpouzis admits that implantation failures
are common, and it is usually possible to determine their causes. Of course, it requires a thorough analysis of a patient’s medical history and the use of tailor-made protocols and advanced diagnostic techniques. Only then doctors can choose available treatments and medications. The best thing to do is to offer the right treatment in the right case or use a combination of treatments. According to Dr Karpouzis, only personalised care and adjusted treatment can bring satisfying results.