In Vitro Fertilisation laboratory action in the event of implantation failure: the embryo.

The aim of in vitro fertilisation (IVF) treatments is to obtain embryos that are able to implant in the mother’s uterus and give rise to a healthy baby. Unfortunately, this is not always achieved, and there are couples who undergo this process repeatedly, which are then considered implantation failures. In these situations it is necessary to reflect and look for alternatives to solve these highly complex cases.

Instituto Bernabeu has a multidisciplinary unit for the treatment of implantation failure that includes doctors, embryologists and molecular biologists, who work together to provide an answer to the question “Why don’t I get pregnant? There are many fronts on which to advance, but in the IVF laboratory we will focus on one of them, the embryo.

Many international studies have been carried out to increase the potential of an embryo to implant in the mother’s uterus. Studies in which we try to optimise the culture media, keep the embryos under observation until the blastocyst stage to select those of better quality (morphology), study the karyotype of the embryo before transfer (chromosomal screening of the embryo), and help the embryo to break the zona pellucida (assisted hatching), among others.

European recommendations for good practice in recurrent implantation failure have recently been published and several ways to increase the chances of achieving pregnancy after embryo transfer have been established. The factors that may be related to the embryo have been analysed and their efficacy in increasing or not the chances of gestation has been assessed. These factors are:

• Blastocyst stage transfer. Blastocyst culture is mandatory, as there is less risk of aneuploidy, better synchronisation with the endometrium and therefore better implantation rates. It may therefore improve pregnancy rates in patients with implantation failure.
• Preimplantation aneuploidy test (PGT-A). In patients with karyotype structural alterations, PGT is recommended for the detection of chromosomal alterations in the embryo. In patients with implantation failure, the use of PGT can be considered to determine the embryo chromosomes and avoid the transfer of chromosomally altered embryos.
• Transfer medium supplemented with hyaluronic acid. The use of transfer medium supplemented with hyaluronic acid could increase pregnancy rates (with limited evidence) as in a study in the general population its use led to an increase in pregnancy rates, although no studies have been conducted in the implantation failure population.

Other techniques rising, although with a low level of evidence are:

• Artificial intelligence tools for embryo evaluation. Sub-optimal embryo development or abnormalities in embryo divisions (morphokinetics) are associated with the embryo low reproductive potential. Artificial intelligence tools could improve embryo selection techniques.
• Sperm selection by microfluidics. Allows sperm selection when a negative effect of the male factor on the embryo is observed.

On the other hand, some other potential techniques have been discarded by European guidelines due to their low level of evidence. These techniques are:

• Mitochondrial DNA content. It has been proposed that mitochondrial DNA content may reflect the viability and implantation potential of the embryo. Recent studies have ruled out this relationship, and mitochondrial DNA assessment is NOT recommended to improve outcomes in patients with implantation failure.
• Assisted hatching. For years it has been thought that the inability of the embryo to escape from the zona pellucida may be related to implantation failure. Several studies have established that assisted hatching does not improve the embryos implantation rates in which it is performed and is therefore not recommended as a routine technique.

Thanks to the clinical recommendations, a roadmap for the treatment of couples with implantation failure can be established, however, a correct and thorough assessment of the case is necessary to determine the origin of the implantation failure and to make the best decisions to achieve the goal of a healthy baby at home.

Dra. Dori Rodríguez, embrióloga del Instituto Bernabeu.