P-764 A decade of transformations in IVF strategies towards enhanced clinical efficacy, efficiency, and safety: the real-life experience of 6610 couples
Authors: Vaiarelli A , Cimadomo D , Innocenti F , Petrone P , Colamaria S , Argento C , Giuliani M , Ferrero S , Maggiulli R , Albricci L , Pittana E , Ruffa A , Capalbo A , Rienzi L , Ubaldi F  M 
Published: July 2024

Abstract

Study question
To what extent do clinical and laboratory strategies affect the main measures of IVF success?

Summary answer
Across 10 years, the implementation and increasing adoption of antagonist protocols combined with agonist-trigger, freeze-all, blastocyst culture, PGT, and multicycle counseling approach improved IVF outcomes.

What is known already
The primary indicator of IVF success is the cumulative-live-birth-rate per intention-to-treat (CLBR per ITT). Since reproductive competence is inherent to every gamete and embryo, IVF treatments cannot guarantee success. However, they can maximize the likelihood of success with the safest approaches available. Furthermore, there are other outcomes to consider for a more thorough assessment of IVF effectiveness and efficiency, including time in treatment (=LB achieved / no LB achieved and no embryo available for transfer; TiT), miscarriage rate, and prevalence of multiple-births. Moreover, a family planning perspective should be strengthened in IVF aiming at ≥ 2 healthy children, whenever feasible.

Study design, size, duration
Longitudinal observation of 6610 couples undergoing ≤6 ovarian-stimulations (OS) for IVF at a private clinic within 3 years. Couples were clustered in 11 groups according to the year of their first treatment (years: 2010-2020) and compared for (i) CLBR within 3 years, (ii) prevalence of ≥ 1 miscarriage and ≥1 twin-delivery, (iii) TiT (from first-OS to the last IVF procedure before treatment conclusion), (iv) prevalence of ≥ 2 singleton-deliveries within 6 years.

Participants/materials, setting, methods
The naïve patients included increased from ≈500 in 2010 to ≥ 600 between 2013 and 2020. The maternal age was stable around 38±4 years with ≈20% prevalence of severe male factor. OS was conducted through long, short flare-up, mild, antagonist, progestin-primed, or DuoStim protocols with hCG/agonist-trigger. All patients underwent ICSI on fresh own eggs and cleavage/blastocyst culture, fresh transfer/freeze-all, untested/euploid transfers, single/multiple-embryo transfers.

Main results and the role of chance
Antagonist-protocols (≈20% in 2010 and ≈80% in 2020) combined with agonist-trigger (0.4% and 76.8%) superseded long/short flare-up (≈60% and &lt;10%) and hCG-trigger (99.6% and 23.2%). DuoStim, introduced in 2015, reached 15%-prevalence by 2020. The MII-oocytes collected at first-retrievals increased from 5±3 (2010) to 7.2±4.9 (2020). The prevalence of first-cycles without embryos raised from 3% to 14% by 2020 primarily due to an evident cleavage-to-blastocyst culture switch (2010:96% versus 4%; 2020:1% versus 99%). Similarly, PGT-A and freeze-all utilization respectively increased from 3% to 80% and from 12% to 93%.
Although TiT increased from ≈2 cycles in ≈140 days (2010-2013) to ≈1.6 in ≈160 days (2014-2020), the 3-years CLBR improved from 32% (2010) to 42% (2020), a difference confirmed also adjusting for maternal age and overall number of MII-oocytes collected (multivariate-OR:1.03,95%CI:1.01-1.05;adjusted-p=0.001). This was paralleled by the halving of women suffering ≥1 miscarriage (≈12% to &lt; 6%;p=0.002) and drop in women with ≥1 twin-delivery (7.5% to 0.5%;p&lt;0.001). The latter achievement was due to single-embryo transfer rates increasing from 26% (2010) to 98% (2020). Accordingly, the women starting in 2017 and obtaining ≥2 LBs within 6-years were 9.9%, 98% of which after consecutive singleton-deliveries; these figures were 6.6% and just 22% among women starting in 2010(p = 0.004).

Limitations, reasons for caution
This study suffers from the inherent limitations of a retrospective design. Temporal changes, other than clinical strategies and laboratory advancements (e.g., personnel), might have influenced the results, although no critical infrastructural changes were implemented. Gestational and neonatal follow-up data are missing in this study.

Wider implications of the findings
Clinical and laboratory advancements enhanced IVF efficacy and efficiency over time also fulfilling family planning desire. Future strategies and improved workflows should focus on reducing drop-out and time-to-LB. As larger oocyte cohorts led to higher CLBR throughout maternal age, tailored-multicycle approach might represent a valuable option to this end.

Trial registration number
none