L26/O-329 Modern IVF clinical practices achieve superior cumulative live birth rates with near-universal single embryo transfer: A multi-cycle cohort study

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Abstract Study question What are contemporary cumulative live birth rates over three IVF cycles using modern clinical practices with near-universal single embryo transfer? Summary answer Modern IVF achieves 68.2% cumulative live birth rate over three cycles with 95.3% single embryo transfer and 2.9% multiple births. What is known already Historical cumulative live birth rate (CLBR) studies preceded adoption of contemporary IVF practices including blastocyst culture, vitrification, freeze-alls, and optimized FET protocols. Earlier studies reporting CLBR included multiple embryo transfers with optimal 3-cycle CLBRs of 53-59%, resulting in multiple pregnancy rates exceeding 20%. International guidelines now recommend single embryo transfer to minimize multiple pregnancies and associated maternal-fetal complications, with some guidelines suggesting preimplantation genetic testing for aneuploidy (PGT-A) may be necessary to achieve acceptable outcomes with SET. However, contemporary multi-cycle CLBR data demonstrating outcomes with near-universal single embryo transfer are lacking, creating uncertainty for patient counseling and healthcare policy development. Study design, size, duration Retrospective cohort study of 18,396 women initiating first IVF cycle between January 2012-December 2021 across seven Australian fertility clinics with follow-up through December 2023. Inclusion criteria: first egg retrieval using autologous oocytes. Exclusion criteria: donor oocytes, frozen oocytes, preimplantation genetic testing for monogenic disorders or structural re-arrangement, gestational carrier. Follow-up through three cycles with retrievals and associated embryo transfers or live birth, whichever occurred first. Participants/materials, setting, methods Women undergoing IVF at seven Australian fertility clinics using standardized protocols including extended blastocyst culture (day 5-6), vitrification, and elective freeze-alls when indicated. Primary outcome: cumulative live birth rate per woman over three initiated cycles analyzed using intention-to-treat (ITT: not adjusted for dropout) and Kaplan-Meier survival analysis (optimal, right-censored for ongoing pregnancies and administratively censored at three cycles). Secondary outcomes: single embryo transfer rate and multiple birth rate. Main results and the role of chance Mean maternal age was 36.2±4.1 years. PGT-A was utilized in one or more cycle for 25% of patients. Overall cumulative live birth rates over three cycles were 58.7% ITT and 68.2% optimal per-protocol analysis. Single embryo transfer was used in 95.3% of all embryo transfers yielding a multiple rate of 2.9%. Optimal 3-cycle CLBR by age group: <35 years 84.5%, 35-37 years 74.4%, 38-40 years 57.7%, 41-42 years 30.1%. Both single-step culture medium and time-lapse culture were introduced in 2016. A sub-analysis of 2012-2015 vs 2017-2021 demonstrated that usable blastocyst rate (48.3 vs 57.6%), optimal CLBR (67.1% vs 69.8%) and SET rate (92.8 vs 97.3%) increased (p < 0.001) while multiple birth rate decreased (3.2 vs 2.7%; p = 0.033). Limitations, reasons for caution Single network retrospective study may limit generalizability. Patient self-selection and physician recommendations influenced treatment continuation decisions. Long-term obstetric and neonatal outcomes were not assessed. Wider implications of the findings Modern IVF clinical optimization achieves higher cumulative live birth rates compared to historical studies where multiple embryo transfer was common, while maintaining reproductive safety through near-universal single embryo transfer. Findings support single embryo transfer policies and demonstrate excellent outcomes achievable without routine preimplantation genetic testing. Trial registration number No

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