Implantation failure has historically been defined as the absence of pregnancy after transfer of three good quality embryos in patients under 40 years of age. Currently the concept of implantation failure has changed, referring to the absence of pregnancy after transfer of three euploid blastocysts in patients without uterine pathology.
It is important to know this definition in order to understand that if the genetic embryonic factor, on the one hand, and the uterine factor, on the other, are not ruled out, we cannot speak of true implantation failure, since this really affects only 5 to 10 % of the patients undergoing assisted reproduction treatment.
Implantation is a complex process in which the embryo and the endometrium play an essential role, although there are co-factors that participate in a more or less obvious way.
What are the causes of implantation failure?
The causes of implantation failure are multiple and are usually distinguished between embryonic, uterine and extrauterine.
Embryonic chromosomal alterations increase in patients over 35 years of age. If the embryos are abnormal, they have a low implantation potential, but if they do implant, they can cause early miscarriages or give rise to fetuses with chromosomal alterations. Currently, the preimplantation genetic study (PGT-A), performed in women over 35 years of age, makes it possible to shorten the time to achieve gestation, reducing the emotional strain linked to repeated failures or miscarriages.
Uterine pathology, on the other hand, affects the implantation potential of the embryo. According to the latest publications, there are different causes that negatively affect the embryo implantation rate:
- Chronic endometritis
- Adenomyosis
- Droughts with or without atrophic endometrium
- Uterine malformations
- Intracavitary polyps or myomas
- Alteration of endometrial receptivity due to displacement of the window of implantation.
Among the extrauterine factors, the structural alteration of one or both tubes (hydrosalpinx) has an extremely negative impact on embryo implantation due to the presence of a toxic liquid inside the tube, which creates a hostile environment for embryo implantation.
Another factor to be taken into account in implantation failure is the alteration of the intrauterine microbial environment which, according to the results of the most recent studies, has a negative impact on the chances of pregnancy. The uterine microbiome is the set of microorganisms that physiologically colonize the uterine cavity. In recent years, much research has been done on this subject and it has been shown that there are deficient lactobacillus profiles related to implantation failure.
Finally, there is the hematological factor, which has a clear impact on repeated miscarriages, although it has not yet been demonstrated that it also has a negative influence on embryo implantation. There is also no conclusive data on the impact of immunological alterations on implantation failure.
Is there a solution for these cases?
It is possible to treat the uterine pathologies mentioned above by antibiotic treatment or surgery. However, the correction of these factors does not ensure implantation, since there are other variables involved that are not yet fully known and which, unfortunately, affect a small percentage of patients who do not achieve pregnancy.
Recently, intrauterine treatment with Platelet Rich Plasma, which is a fraction of blood containing a high concentration of growth factors with an endometrial regenerative effect, has begun to be proposed to these patients.
The evidence of its benefits in many fields of medicine, such as vascular surgery, ophthalmology, aesthetics, traumatology and sports medicine, is very high. However, in assisted reproduction its use is very recent and there are still no certain results on its efficacy in implantation failure.
The published studies are positive and describe an increase in the pregnancy rate in patients with implantation failure. Moreover, it is a safe treatment with no risk of rejection or allergy, so it could be a hopeful therapeutic possibility for those patients with unexplained implantation failure.