P–755 Perinatal outcomes following Day–4 embryo transfer compared to Day–2, Day–3 and Day–5 embryo transfer: an analysis of 56,346 singleton live births
Authors: Sfontouris I , Nikiforaki D , Sialakouma A , Liarmakopoulou S , Matzakou I , Koutsi A , Polia A , Belmpa M , Maalouf W , Hernandez-Medrano J 
Published: August 2021

Abstract

Study question
Are perinatal outcomes of singleton live births following Day–4 embryo transfer (ET) different to Day–2, Day–3 and Day–5 ET?

Summary answer
Perinatal outcomes of singleton live births following Day–4 ET are similar with those following Day–2, Day–3 and Day–5 ET.

What is known already
The morula represents a critical stage in preimplantation embryo development, but the usage of morula transfer on Day–4 has received little attention. Recent work from our group suggested that live birth rates following Day–4 ET appear higher than cleavage-stage ET, but lower than blastocyst ET. Therefore, Day–4 appears an alternative day to perform ET, offering the benefits of extended culture for embryo selection, but with shorter in-vitro culture exposure, as well as improving flexibility and planning in the IVF Clinic. However, there are extremely limited data available on the perinatal outcomes after Day–4 ET compared to cleavage-stage and blastocyst ET.

Study design, size, duration
Retrospective cohort study using data from the anonymised dataset of the Human Fertilisation and Embryology Authority (HFEA) in the UK between 2000 and 2016. Data from singleton live births of women undergoing their first IVF/ICSI cycle were analysed to compare perinatal outcomes after fresh Day–2,3,4,5 embryo transfers.

Participants/materials, setting, methods
Births resulting from the first, fresh, autologous, stimulated, non-PGT cycles, with full data, were included. After exclusions, a total 56,346 singleton live births were included in the analysis (17,613 from Day–2 ET, 15,533 from Day–3 ET, 508 from Day–4, 22,692 from Day–5 ET).
Binary/multinomial logistic regression analysis was performed to adjust for important cofounders. Adjusted odds ratios (aORs) and 95% confidence intervals (95%CI) were calculated. The level of significance was set at &lt; 0.05.

Main results and the role of chance
The probabilities of birth at full-term (FT) and normal birthweight (NBW) after Day–4 transfer (FT 90.4%; NBW 84.6%) were similar to Day–2 (FT 89.7%, aOR 0.994, [0.734–1.344]; NBW 81.9%, aOR 0.881, [0.708–1.096]), Day–3 (FT 90.2%, aOR 1.026, [0.760–1.386]; NBW 82.4%, aOR 0.894, [0.719–1.111]) and Day–5 transfer (FT 90.4%, aOR 1.001, [0.743–1.350]; NBW 83.7%, aOR 0.920, [0.741–1.142]).
The probabilities of preterm birth (PTB) and very preterm birth (VPTB) after Day–4 transfer (PTB 9.3%; VPTB 0.4%) were similar to Day–2 (PTB 9.5%; aOR=0.952; VPTB 0.8%; aOR=2.172), Day–3 (PTB 9.0%, aOR=0.920; VPTB 0.9%, aOR=2.174), and Day–5 transfer (PTB 8.8%; aOR=0.955; VPTB 0.8%, aOR=1.956).
The probabilities of very-low birthweight (VLBW), low birthweight (LBW), high birthweight (HBW) and very-high birthweight (VHBW) after Day–4 transfer (VLBW 0.9%, LBW 7.9%, HBW 6.3%, VHBW 0.3%) were similar to Day–2 (VLBW 1.8%, aOR=1.827; LBW 8.0%, aOR=1.015; HBW 8.1%, aOR=1.174; VHBW 0.2%, aOR=0.590), Day–3 (VLBW 1.8%, aOR=1.788; LBW 7.4%, aOR=0.927; HBW 8.3%, aOR=1.256; VHBW 0.2%, aOR=0.503) and Day–5 transfer (VLBW 1.6%, aOR=1.782; LBW 6.9%, aOR=0.894; HBW 7.5%, aOR=1.215; VHBW 0.2%, aOR=0.796).
The probability of having a female baby after Day–4 transfer (51.6%) was similar to Day–2 (49.2%, aOR 0.940), Day–3 (49.3%, aOR 0.931) and Day–5 transfer (48.3%, aOR 0.869).

Limitations, reasons for caution
The study is limited by its retrospective nature, the inability to adjust for additional confounders and the small number of singleton births after Day–4 ET. It is not known how Day–4 ET was decided. The incidence of congenital abnormalities was not analysed due to incomplete registration in the dataset.
Wider implications of the findings: Perinatal outcomes of singleton live births following Day–4 ET are similar with those following Day–2, Day–3 and Day–5 ET, suggesting that morula transfer is equally safe as cleavage-stage and blastocyst transfer. Data on a larger number of live births from well-designed RCTs are required to confirm these findings.

Trial registration number
Not applicable