Abstract Study question What is the likelihood of pregnancy in successive IVF attempts, and how does it relate to the concept of recurrent implantation failure? Summary answer The first two IVF transfer attempts have the highest pregnancy chances, while subsequent attempts show stability, challenging the notion of recurrent implantation failure. What is known already According to the theory of recurrent implantation failure (RIF), around 10% of patients undergoing several embryo transfers fail to implant due to certain risk factors. This should eventually enrich this subset as more transfers are performed. According to conventional thinking, this group’s IVF success rates should therefore soon start to significantly fall. Recent studies on euploid embryo transfers, however, have started to challenge this idea. They suggest that the IVF success rate drop may be less than previously believed, and that RIF may be less prevalent than previously expected. Study design, size, duration This registry study of the Danish IVF registry used historical data from 1994 to 2019, comprising a large cohort of 85,453 unique women who underwent 171,159 transfers. Participants/materials, setting, methods A participant could receive up to ten transfers in a row. The live birth rate (LBR) for every transfer cycle, as well as the cumulative LBR was calculated. After achieving a pregnancy, the woman was censored. The mean age of the patients included in the study was 33.8 (33.7-33.8) years at the time of the first ovarian stimulation with a mean BMI of 24.2 kg/m2. Main results and the role of chance The median number of stimulations was 2 and a total median number of 8 oocytes were obtained per patient. The first two transfer-attempts had the highest LBR, with 38.48% and 33.99%, respectively. Subsequent attempts showed a gradual decline but maintained relative stable: the LBR was 30.61% in the third attempt, followed by 28.00% for the fourth and 27.14% for the fifth attempt.Beyond the fifth attempt, the success rates were around 25%. Moreover,we conducted an analysis of 25,433 transfers performed from 2017-2019 transfers, predominantly involving blastocyst-transfers. Herein, the LBRs were higher: 42.31% in the first attempt and 37.81% in the second attempt. Like in the whole cohort, subsequent cycles demonstrated a gradual decline in LBR, however with the 8th attempt still yielding 28.87%. Notably, cumulative live birth rates (CLBR) revealed a steady increase for those having enough blastocysts to transfer: By the fifth attempt, the CLBR had reached 89.86%, and this trend continued to rise, culminating in 98.40% CLBR after the tenth attempt. These findings challenge the conventional notion of RIF,as they suggest that, while a slight decline in LBR is evident with additional IVF attempts, the cumulative chances of achieving a livebirth remain substantial for patients able to pursuing multiple cycles. Limitations, reasons for caution As a retrospective register study, we relied on historical data from 1994 to 2019. It does not take potential changes in clinical practices over time or patient-specific factors that may influence fertility, such as age, underlying conditions, or specific treatment protocols into account. Wider implications of the findings Our findings challenge the conventional understanding of RIF in IVF. The consistency of pregnancy rates over several transfers may have significant effects on patient counseling and clinical practice. Understanding that IVF success is possible even after multiple attempts may reduce anxiety, making informed decisions for couples pursuing reproductive treatments easier. Trial registration number not applicable
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