The OPERA project: a harmonized multinational real-world ART database across Italy and Germany (2016-2020) and a...

Assisted reproductive technology (ART) practice varies widely across centers and evolves rapidly, often outpacing the generation of randomized evidence. OPERA (Observational ProjEct for a Research database for ART procedures) was developed to create a harmonized, multinational real-world database derived from routine clinical ART documentation and to provide a structured overview of contemporary clinical practice.

OPERA is a retrospective, multicenter database including 18 IVF/ICSI centers (9 in Italy and 9 in Germany) using a shared electronic platform (Meditex). All second- and third-level ART cycles performed between January 1, 2016 and December 31, 2020 were eligible for inclusion. Data were extracted from Meditex, harmonized into four relational domains (Baseline, Stimulation, Laboratory, and Pregnancy outcomes), and anonymized prior to aggregation. After data cleaning (duplicate removal, exclusion of unlinked frozen embryo transfer cycles, and cycles with incomplete follow-up), 64,081 ovarian stimulation cycles and 31,027 intended frozen embryo transfer cycles were included. Analyses were descriptive, and no imputation was performed.

Median female age was 37 years (IQR 33-39), and median BMI was 22.7 kg/m². Antagonist protocols were used in 78.4% of cycles. Clinical pregnancy rates were 33.8% for fresh embryo transfers and 34.2% for frozen embryo transfers, with corresponding live birth rates of 25.8% and 24.3%.

OPERA provides a large, harmonized real-world ART dataset enabling a comprehensive overview of clinical practice across multiple centers. While the descriptive design does not allow causal inference, it supports benchmarking and hypothesis generation for future analytical studies, acknowledging inherent limitations related to variable completeness and privacy-preserving data structure.