L26/P-442 Evolution of ART in Italy: analysis of 1.8 million cycles over 20 years from the Italian ART Registry

Abstract Study question What is the status and evolution of ART in Italy 20 years after the implementation of Law 40/2004? Summary answer Twenty years after Law 40/2004, ART in Italy has evolved substantially, with increased availability, improved efficacy and safety, faced changes following legislative and scientific-technological developments. What is known already In Italy the Law 40/2004 regulates Medically Assisted Reproductive techniques in Italy and the subsequent Decree of Minister of Health (2005) established the Italian ART Registry (IARTR) at the italian National Institute of Health. Law 40/2004 was initially particularly restrictive and was subsequently amended by four rulings of the Italian Constitutional Court sentences. These rulings abolished limits on embryo production and transfer (2009), removed the ban on gamete donation (2014), lifted restriction on access to preimplantation genetic testing for fertile couples with transmissible genetic diseases and abolished the ban on embryo selection to avoid the implantation of affected embryos (2015). Study design, size, duration Data collection for the IARTR has been mandatory by law since 2005. Data are collected retrospectively in aggregated form through an electronic web-based system, including over 1,800 variables describing the ART activity in Italy. A retrospective data analysis of the first 20 years of IARTR activity was conducted, based on more than 1.8 million cycles, to epidemiologically evaluate the evolution of ART in Italy. Participants/materials, setting, methods Since 2005, IARTR has achieved complete coverage of all active centres, ART cycles and pregnancies obtained in Italy. A total of 1,387,357 ART cycles, performed in 1,152,705 patients were reported, including IVF, ICSI, Frozen Embryo Replacement, frozen/warmed oocyte and gametes donation. Additionally, 463,636 intrauterine insemination (IUI) cycles using partner or donor semen were recorded. The 1,850,993 cycles resulted in the birth of 252,170 infants, of which 217,661 from ART techniques. Main results and the role of chance Between 2005 and 2024, ART activity increased 2.8-fold, while IUI activity decrease by approximately 60% from 2012 onwards. ART availability rose from 2,683 cycles per million of inhabitants in 2005 to 10,388 in 2024. The proportion of infants born following ART increased from 7‰ to 45‰ of all live births in Italy. The proportion of women aged ≥40 years undergoing an IVF/ICSI increased, as did the use of frozen versus fresh embryos transfers since 2010. The proportion of ART transfer with 3 or more embryos rapidly decline from 2010, while single embryo transfers steadily increased over the same period. Treatments efficacy improved for FER and FO and remained quite stable for IVF/ICSI. Cumulative pregnancy rate per retrieval constantly increases over time. Because of the constant reduction of the mean number of embryos transferred, multiple deliveries rates declined from 22.9% in 2009 to 3.8% in 2024. The incidence of adverse perinatal outcomes, including congenital anomalies, low birth weight, preterm birth and neonatal mortality also decreased. Limitations, reasons for caution Although the IARTR achieves complete coverage of ART activity in Italy every year, the retrospective and aggregated nature of the data collected allows limited to macro-level epidemiological trends. Additionally, despite pregnancy lost to follow-up rate remain below 10% in recent years, outcomes for all ART pregnancies cannot be fully ascertained. Wider implications of the findings This is the first summary of 20-year overview of IARTR activity since the introduction of Law 40/2004. The IARTR has monitored the application of ART techniques in Italy, documents the impact of legislative changes, outlined scientific and technological progress and national trends in ART availability, efficacy and safety in Italy. Trial registration number No