Infertility is defined as the inability of a couple to achieve pregnancy within one year, affecting approximately 10% of European couples. More than half of these couples rely on in vitro fertilisation (IVF) treatments, the majority of which do not result in a live birth, foremost as a result of poor embryo attachment to the womb lining leading to implantation failure. Embryos with abnormal chromosomal constitution, so-called aneuploid embryos, are accountable for approximately 50% of all recurrent implantation failures after IVF in women >35 years old. Preimplantation Genetic Testing for aneuploidy (PGT-A) is an add-on treatment proposed to IVF couples with advanced maternal age and/or those who repeatedly fail to achieve implantation. PGT-A is an early form of prenatal genetic diagnosis where aneuploid embryos are identified and only normal (euploid) embryos are selected for transfer into the womb in order to increase implantation probability. Although the patient access to PGT-A is rising, the technology itself is highly controversial; it requires an invasive biopsy of the embryo cells, which evidently decreases embryo quality. At the same time, the long-term safety of embryo biopsy in humans has not yet been evaluated. Thus, the development of non-invasive methods to screen out aneuploid embryos is paramount. However, since the other half of all implantation failures is attributed to unexplained causes, it is also critical to understand what biological mechanisms promote successful attachment of embryos to the womb lining.
Importance: PGT-A is an integral part of IVF procedures and increasing number of clinics perform embryo biopsy to all embryos regardless of indication only to ensure a euploid embryo is transferred to the womb, which hypothetically should decrease the time that a couple becomes a parent. PGT-A add-on is extremely costly and doubles the overall cost of conventional IVF due to the expertise required to perform embryo biopsy and the collateral costs like embryo freezing. Moreover, embryo biopsy has not been evaluated for long-term impacts on the offspring and it does not guarantee success as even in the case when a healthy embryo is transferred to the womb, it can still be rejected. Hence, less invasive and cheaper therapeutic options to diagnose embryos are in high demand and will make a tremendous impact on IVF practice. Finally, understanding why the womb rejects healthy embryos will help to better manage couples suffering for recurrent implantation failure.
Objectives: Our research project aimed a) to discover non-invasive biomarkers of embryo aneuploidy by studying the compounds that embryos secrete while growing in culture and b) describe a biological mechanism by which aneuploid embryos may stimulate a rejection response in the womb lining by exploring the feedback of womb cells to the internalisation of the aneuploid embryo-secreted compounds.
