Michael Kiriakidis, MD, Msc , IVF Specialist, Deputy Scientific Director Embryolab IVF Clinic
The advancement of technology and knowledge in assisted reproduction over the last decades has significantly increased the chances of success and helped millions of couples worldwide in starting their families. However, some couples may not achieve pregnancy despite repeated attempts at embryo implantation.
Embryo implantation is a critical step in human reproduction. The successful implantation of an embryo depends on various factors, including the embryo’s dynamics, the receptivity of the endometrium, and the interaction between them. In an effort to explain the problem of repeated implantation failures, the European Society of Human Reproduction and Embryology (ESHRE) recently published guidelines for managing this puzzle.
According to the latest data, defining the problem should be personalized for each couple. The suggested threshold is two failed embryo transfers, taking into account the couple’s age and the morphological characteristics of the embryos. Since all couples have already undergone preliminary screening before starting treatment, certain data should be re-evaluated in this case.
Initially, a thorough reevaluation of the uterus should be conducted, including both the endometrium and the muscular wall. This examination should confirm the thickness and morphology of the endometrium and exclude the presence of endometrial pathology or any other issues in the main body of the uterus (e.g., fibroids) that may have developed. This assessment should include three-dimensional ultrasound and hysteroscopy. At this stage, the couple may choose to undergo some functional tests as well. The examination of choice is endometrial biopsy and histological evaluation, in order to identify inflammatory markers, immunological factors as well as a disbalance of the uterine microbiome.
The next phase involves a reassessment of the couple’s lifestyle and specific physical characteristics. Improving dietary habits, weight loss if needed, improving sleep pattern, and quitting smoking can make a significant difference in the subsequent treatment cycles for the couple.
In a subsequent phase, specialized metabolic and genetic examinations should be included. Although such problems are considered quite rare, it is worth excluding the involvement of these factors in previous failures. Therefore, a detailed check of thyroid function, glucose metabolism, and the patient’s hormonal profile is necessary before modifying the therapeutic plan. In this phase, the value of functional examinations that can be performed in the endometrium (such as the endometrial receptivity assessment, ERA test) should also be reviewed.
Finally, the importance of preimplantation genetic testing of embryos (PGT-A/PGT-M/PGT-SR) should be mentioned to avoid future implantation failures. This testing is a clinical tool for assessing the chromosomal profile of a couple’s embryos. While there are legal criteria for performing this test, many couples may benefit, so it should be included in the treating physician’s toolkit.
Recurrent implantation failures have been correlated with increased stress levels and the accumulation of feelings of disappointment in couples. For this reason, psychological support and well-documented guidance are considered essential elements in addressing this particular situation. Our guidelines provide a significant strategic pathway for exploring a challenging puzzle and a solid foundation for addressing the issue of recurrent implantation failures in in vitro fertilization.
