Cost effectiveness of routine utilisation of atypically-pronucleated zygotes in IVF cycles with preimplantation genetic testing

Objective: To evaluate the cost-effectiveness of including embryos derived from atypically-pronucleated zygotes (APZs) in IVF cycles with preimplantation genetic testing for aneuploidy (PGT-A), compared with standard use of only typically fertilised (2PN) embryos. Design: Model-based cost-effectiveness analysis using retrospective clinical data. Subjects: Data were derived from two clinical embryology datasets from a private IVF centre in Italy, comprising 8,334 intracytoplasmic sperm injection (ICSI) cycles with PGT-A (2015-2022) and 826 ICSI cycles with time-lapse monitoring (2013-2020). Exposure: A decision-tree model compared two IVF strategies over up to two treatment cycles: (1) standard selection of euploid blastocysts derived exclusively from 2PN zygotes and (2) inclusion of PGT-A-confirmed euploid blastocysts derived from APZs (1PN or ≥3PN) in addition to 2PN embryos. Main outcome measures: The primary effectiveness outcome was the probability of achieving at least one live birth per treatment pathway, and costs reflected patient out-of-pocket expenses. Incremental cost-effectiveness ratios (ICERs) were calculated against a patient-derived willingness-to-pay (WTP) threshold of €422.25 per 1% absolute increase in live-birth probability. Deterministic (±20% parameter variation) and probabilistic (10,000 Monte Carlo simulations) sensitivity analyses evaluated parameter uncertainty and the robustness and transferability of results across clinical and economic settings, with subgroup analyses by maternal age and embryo availability. Results: Inclusion of APZ-derived euploid blastocysts increased cumulative live-birth probability from 0.7294 to 0.7436 (absolute increase 1.42%) while marginally reducing mean treatment cost (€12,737.92 vs €12,749.49), resulting in a cost saving of €11.57 per couple. Across all sensitivity analyses and subgroups, the APZ-inclusive strategy consistently demonstrated higher effectiveness with lower costs or favourable ICERs, remaining economically dominant or cost-effective within the predefined WTP threshold. Notably, higher treatment costs further enhanced the relative cost-effectiveness of APZ utilisation by increasing the economic value of incremental gains in live-birth probability. Conclusions: Inclusion of PGT-A-confirmed euploid APZ-derived blastocysts improves IVF live-birth outcomes at lower or comparable cost and remains cost-effective across diverse clinical and economic scenarios. This is particularly relevant in healthcare systems with higher IVF and PGT-A costs, supporting routine integration of APZ-derived embryos as a generalisable and economically efficient approach.