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What is repeated embryo implantation failure?
The pathology of repeated embryo implantation failure is diagnosed in a woman undergoing fertility care when she has several unexplained implantation failures. However, there is no clear, official definition of this condition. Each centre determines a stage at which it is considered abnormal that none of the embryos transferred has implanted. The majority of practitioners consider that a patient is suffering from repeated embryo implantation failure when no implantation has been diagnosed after the transfer of at least three embryos with a high implantation potential.
Failure of the embryo to implant
Embryo implantation is diagnosed around ten days after the transfer by measuring a hormone: β-hCG. One month later, the presence of a gestational sac developing within the uterine cavity must be confirmed by ultrasound.
The medical team, therefore, refers to embryo implantation failure when the β-hCG assay is negative or when the ultrasound examination does not reveal the presence of an embryo in the endometrium.
Embryo implantation failures: embryonic causes
Repeated embryo implantation failures can have many causes. Increasingly, the quality of the embryos themselves is being called into question by the medical profession. It is thought to be the main cause of embryo implantation failures.
The main cause: a genetic anomaly in the embryo
During a fertility protocol, the implantation potential of the embryos is estimated by morphological analysis. This does not reveal any potential genetic problems (abnormal number of chromosomes, gene mutations, DNA alterations, etc...).
However, genetic abnormalities in the embryo are the main cause of implantation failure. They are linked to a poor-quality oocyte and/or spermatozoon.
Factors in genetic anomalies of the embryo
Various factors can influence the quality of gametes (oocytes and spermatozoa). These may be endogenous factors such as age or body mass index, for example. A high age, overweight, or even obesity are responsible for oocyte and sperm abnormalities. On the other hand, exogenous factors such as exposure to toxic molecules (tobacco, endocrine disruptors, etc.) affect the quality of female and male gametes.
Thus, an embryo may be judged to be of good quality "morphologically" but not "genetically". Only a pre-implantation diagnosis of the embryo can identify potential genetic anomalies in the embryo. At present, this technique is only offered to couples who are likely to pass on a genetic disease to their children.
Embryo implantation failures: uterine causes
The embryo is not the only cause of implantation failure. In fact, an embryo with high implantation potential from a morphological and genetic point of view will not be able to implant if the endometrium is not receptive to it. A number of pathologies and uterine malformations disrupt the uterus' receptiveness to the embryo.
1. Menstrual cycle abnormalities
During the menstrual cycle, the endometrium undergoes a phase of regression followed by regeneration and maturation. A mature endometrium will be receptive to the embryo during a short period known as the "implantation window". Abnormalities in the menstrual cycle may be responsible for a defect in endometrial regeneration and/or maturation. In this way, the endometrium will not be thick enough or will not be receptive to the embryo.
2. Uterine congenital malformations
During the foetal period and the development of the female reproductive system, developmental abnormalities can cause uterine malformations. These can result in a bicornuate or septate uterus, which can interfere with embryo implantation.
3. Immunological disorders
During embryo implantation, the maternal immune system plays a fundamental role. Failed implantation can be explained by an overly aggressive immune response that leads to the death of the embryo, which is recognised as a foreign body. Conversely, a reduced uterine immune response compromises adhesion between the embryo and the endometrium.
4. Endometrial pathologies
Endometriosis, fibroids, polyps, infections, hydrosalpinx... All these pathologies affect the quality of the endometrium and can lead to embryo failure and infertility.
Care for women suffering from repeated embryo implantation failures due to endometrial causes is complicated. There are many treatments (medicinal or surgical). They are personalised according to the disorder observed and the patient's history.
The pathology of repeated embryo implantation failures is therefore difficult to understand, as the causes may be multiple. Although the embryo is the main cause of these failures, uterine anomalies that can compromise the implantation process should not be overlooked.
Written by:
Fabien Duval, Ph.D.
Reproductive and Developmental Biology
