PEStimate: predicting offspring disease risk after polygenic embryo screening

Area of Science:

• Genetics
• Reproductive Medicine
• Bioinformatics

Background:

• Polygenic embryo screening (PES) is a novel technology for assessing genetic risk of complex diseases in IVF embryos.
• Current PES models often rely on epidemiological predictions and may not account for all factors influencing outcomes.
• Previous models have not incorporated the possibility of embryo implantation failure, potentially leading to overestimated risk reductions.

Purpose of the Study:

• To develop and present PEStimate, a user-friendly online application for predicting the outcomes of polygenic embryo screening for single-gene disorders.
• To provide a tool that allows for a more accurate estimation of risk reduction by incorporating embryo implantation failure.
• To enable stakeholders to better evaluate the potential benefits and harms of PES.

Main Methods:

• Development of an online application, PEStimate, accessible via a web link.
• Implementation of a model that predicts offspring risk with and without PES, considering various user-adjustable parameters.
• Inclusion of embryo implantation failure as a novel factor in the risk prediction model.

Main Results:

• PEStimate generates predictions of offspring disease risk and visualizes risk reduction across different parameters.
• The model demonstrates that previous risk reduction estimates for PES may have been overestimated due to the exclusion of implantation failure.
• The tool allows customization based on factors like embryo availability, live birth rates, disease prevalence, and parental genetic information.

Conclusions:

• PEStimate offers a more realistic assessment of polygenic embryo screening outcomes by incorporating embryo implantation failure.
• This tool is valuable for geneticists, healthcare professionals, and patients in understanding the impact of PES.
• The application facilitates informed decision-making regarding the use of PES by weighing potential benefits against societal and personal harms.