Effectiveness and safety of consecutive single embryo transfer compared to double embryo transfer: results from the UK HFEA registry.

study questionHow does two-consecutive single embryo transfer (2xSET) affect reproductive outcomes of IVF and ICSI compared to double embryo transfer (DET)? SUMMARY ANSWER: Two-consecutive SET may provide greater or comparable live birth rate (LBR); with lower multiple birth, preterm birth, and pregnancy loss or neonatal death rates compared to DET. WHAT IS KNOWN ALREADY: Elective SET in IVF/ICSI is widely encouraged over DET to minimize the risk of multiple births and associated morbidities. Despite this, multiple birth rates following IVF remain higher than the 10% target across Europe and the USA. Currently, the majority of evidence regarding SET and DET is based on various studies assessing outcomes such as LBR per treatment cycle, as opposed to per oocyte retrieval. As such, the representation of SET is mostly unfavourable. Analysis of cumulative LBR following the transfer of two embryos over consecutive cycles, rather than in one transfer event (DET) is more effective at distinguishing the two methods and will therefore provide more valuable information relevant to clinical practice. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study was conducted using Human Fertilisation and Embryology Authority (HFEA) register data, which encompasses national data from all IVF clinics in the UK. All women who underwent their first oocyte retrieval and IVF or ICSI treatment cycle with subsequent SET, DET, or 2xSET between 2010 and 2019 using blastocyst embryos were included (N = 71 807). PARTICIPANTS/MATERIALS, SETTING,

methodsThe rate of live birth, liveborn baby rate, multiple birth, preterm birth, and pregnancy loss or neonatal death was compared between SET, DET, and 2xSET IVF/ICSI pregnancies using blastocyst-stage embryos, where data were stratified by maternal age. Data analysis was conducted in RStudio v4.2, alpha equals 0.05. MAIN RESULTS AND THE ROLE OF CHANCE: Blastocyst-stage 2xSET achieved a greater median LBR of 0.47 (interquartile range [IQR] 0.13) than SET, 0.41 (IQR 0.13), and DET, 0.38 (IQR 0.13) (P < 0.05). Using SET as the reference standard, 2xSET was associated with a significantly lower odds of multiple births compared to DET ((odds ratio [OR] 6.87, 95% CI 6.14-7.68) vs 28.20, 95% CI 25.20-31.57). The odds of preterm birth were also lower following 2xSET (OR 1.11, 95% CI 1.06-1.15) compared to DET (OR 2.80, 95% CI 2.67-2.94). Similarly, the odds of pregnancy loss or neonatal death were lower following 2xSET (OR 1.14, 95% CI 1.08-1.21) compared to DET (OR 2.11, 95% CI 1.98-2.24). LBR was consistently higher following 2xSET than DET and SET in women aged 39 years and under (P < 0.05). However, results were comparable in women over 39 years (P > 0.05). Across all age groups, DET pregnancies had the highest multiple birth rate (P < 0.05). In women aged 39 years and under, DET was associated with the highest preterm birth rate (P < 0.05), whereas the rate was comparable across cohorts in women over 39 (P > 0.05). Moreover, pregnancy loss and neonatal death rates were highest following DET in women aged 37 years and under (P < 0.05), and comparable to SET and 2xSET in women over 37 years (P > 0.05). LIMITATIONS, REASONS FOR CAUTION: Certain confounders are not recorded within HFEA registry data, including patient BMI, evaluation of embryo quality, and endometrial thickness at embryo transfer. Consequently, while our analysis identifies broad trends in embryo transfer success and morbidity, results may differ within certain patient populations. WIDER IMPLICATIONS OF THE

findingsBlastocyst-stage 2xSET may provide greater LBR in women aged 39 years and under, and comparable LBR in women over 39 years old, with overall lower multiple birth and morbidity than DET. 2xSET should be considered first-line among certain patient cohorts, including women with advanced maternal age to improve reproductive outcomes and reduce the risk of morbidity following ART. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. None of the authors has any conflicts of interest. TRIAL REGISTRATION NUMBER: This cohort study did not require registration. Following consultation with the Institutional Review Board at Imperial College London, ethical approval was not deemed necessary.