P-745 effectiveness and safety of consecutive single embryo transfer compared to double embryo transfer: results from UK HFEA registry
Authors: Tighe J , Broughton S , Kasaven L , Cutting R , Bridges E , Ng A , Evans A , Theodorou E , Ben Nagi J , Jones B 
Published: July 2024

Abstract

Study question
How does two-consecutive single embryo transfer (2xSET) affect reproductive outcomes of in-vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) compared to double embryo transfer (DET)?

Summary answer
2xSET may provide greater or comparable live birth rates with lower multiple birth, preterm birth, and pregnancy loss or neonatal death rates compared to DET.

What is known already
Elective single embryo transfer (SET) in IVF/ICSI is widely encouraged over DET to minimise the risk of multiple birth and associated morbidities. Despite this, UK multiple birth rates following IVF remain higher than spontaneous conception, with 5% of IVF pregnancies resulting in multiple birth compared to 0.4%-1.2% multiple gestation rates following spontaneous conception.
Owing to advancements in cryopreservation techniques, live birth and ongoing pregnancy rates are now comparable between fresh and frozen embryo transfer. Consequently, 2xSET has been suggested as an alternate technique to achieve comparable live birth rates with fewer multiple gestation pregnancies compared to DET.

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. Within this analysis, all women who underwent their first oocyte collection and IVF or ICSI treatment cycle with subsequent SET, DET or 2xSET between 2010 and 2019 using either blastocyst or cleavage stage embryos were included (N = 125,149).

Participants/materials, setting, methods
This national retrospective cohort study utilised UK HFEA register data from 2010-2019, including all women who underwent their first oocyte collection and subsequent embryo transfer (N = 125,149). The rate of live birth, multiple birth, preterm birth, and pregnancy loss or neonatal death was compared between SET, DET, and 2xSET IVF/ICSI pregnancies using either blastocyst or cleavage stage embryos, and was stratified by maternal age. Data analysis was conducted in RStudio v4.2, alpha equals 0.05.

Main results and the role of chance
2xSET pregnancies following blastocyst-stage transfer achieved a greater live birth occurrence rate of 0.47 (0.13) (median (interquartile range)) than SET, 0.41 (0.13), and DET, 0.38 (0.13) (P &lt; 0.05). When using SET as a reference standard, 2xSET achieved a lower multiple birth rate, odds ratio (OR) of 6.87 (95%CI 6.14-7.68), than DET, OR 28.20 (95%CI 25.20-31.57), and lower preterm birth rate; OR 1.11 (95%CI 1.06-1.15) in 2xSET, and OR 2.80 (95%CI 2.67-2.94) in DET. Pregnancy loss or neonatal death rate was also lower in 2xSET, OR 1.14 (95%CI 1.08-1.21), compared to DET, OR 2.11 (95%CI 1.98-2.24).
Conversely, in cleavage-stage embryo transfer pregnancies, no significant difference in live birth occurrence rate was observed, achieving rates of 0.27 (0.21) for SET, 0.26 (0.13) for DET, and 0.29 (0.18) for 2xSET. 2xSET was less likely to result in multiple birth than DET, OR 0.14 (95%CI 0.11-0.19). Moreover, when using SET as a reference standard, 2xSET was less likely to result in preterm birth than DET, OR 1.02 (95%CI 0.87-1.23) and 2.48 (95%CI 2.17-2.82) respectively, as well as pregnancy loss or neonatal death, OR 1.07 (95%CI 0.85-1.35) and 2.03 (95%CI 1.70-2.42) respectively.

Limitations, reasons for caution
Certain confounders are not recorded within HFEA registry data, including patient body mass index (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 findings
2xSET may provide greater or comparable live birth rates with lower multiple birth and morbidity than DET. Promotion of 2xSET where appropriate for maternal age and embryo quality should be implemented to enhance reproductive outcomes and reduce the risk of morbidity in IVF/ICSI pregnancies.

Trial registration number
Not Applicable