Modeling polygenic embryo screening in real-world IVF patients demonstrates limitations on efficacy

Area of Science:

• Reproductive genetics
• Genomic risk assessment
• In-vitro fertilization (IVF)

Background:

• Polygenic embryo screening (PES) evaluates embryo genetic risk for complex diseases.
• Initial models predicted substantial disease prevalence reduction.
• Realistic IVF outcomes, including live birth rates, were not fully considered in prior models.

Purpose of the Study:

• To quantify the actual risk reduction achievable with PES in IVF settings.
• To compare PES effectiveness considering real-world IVF success rates.
• To assess PES benefits across different patient groups and cycle types.

Main Methods:

• Utilized datasets from 4452 Italian infertility patients and 2138 egg donors.
• Simulated PES application by assigning random polygenic risk scores to embryos.
• Analyzed birth outcomes based on simulated embryo transfers and real-world IVF data.

Main Results:

• Infertility patients: 1-3% risk reduction in completed cycles with live births; <0.5% in intention-to-screen analysis.
• Risk reductions increase with more euploid blastocysts and younger maternal age.
• Egg donor cycles show up to 20% risk reduction, higher than infertility patients.

Conclusions:

• Typical infertility patients show limited benefit from PES due to low IVF success rates.
• Fertile populations like egg donors demonstrate greater, yet still reduced, risk reductions compared to initial estimates.
• Further research on ethical, social, and clinical implications of PES is crucial.