Perinatal outcomes in singleton live births after fresh blastocyst-stage embryo transfer: a retrospective analysis of 67 147 IVF/ICSI cycles.

Study Question: Are perinatal outcomes different between singleton live births conceived from fresh blastocyst transfer and those following the transfer of fresh cleavage-stage embryos?

Summary Answer: Fresh blastocyst transfer does not increase risks of preterm birth (PTB), low/high birth weight or congenital anomaly and does not alter the sex ratio at birth or prejudice the chance of having a healthy baby.

What Is Known Already: Extended embryo culture is currently considered the best option for embryo selection, but concerns have been raised about increased risks of preterm delivery and large-for-gestational-age (LGA) babies.

Study Design, Size, Duration: We conducted a retrospective cohort study based on data from the Human Fertilisation and Embryology Authority (HFEA) anonymised and cycle-based dataset in the UK between 1999 and 2011.

Participants/materials, Setting, Methods: Baseline characteristics were compared between in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) blastocyst-stage and cleavage-stage embryo transfer cycles using the χ2 test for categorical/dichotomised covariates and the Mann-Whitney test for continuous covariates. Statistical significance was set at <0.005. Poisson regression and multinomial logistic regression were used to establish relationships between perinatal outcomes and blastocyst-stage embryo transfer or cleavage-stage embryo transfer. Risk ratios (RRs), adjusted risk ratios (aRRs) and their 99.5% confidence intervals (CIs) were calculated as a measure of strength of associations. Results were adjusted for clinically relevant covariates. A sub-group analysis included women undergoing their first IVF/ICSI treatment. The level of significance was set at <0.05, and 95% CIs were calculated in the sub-group analysis.

Main Results And The Role Of Chance: Of a total of 67 147 IVF/ICSI cycles, 11 152 involved blastocyst-stage embryo(s) and 55 995 involved cleavage-stage embryo(s). The two groups were comparable with regards to the risk of PTB (aRR, 1.00; 99.5% CI, 0.79-1.25), very-preterm birth (VPTB) (aRR, 1.00; 99.5% CI, 0.63-1.54), very-low birth weight (VLBW) (aRR, 0.84; 99.5% CI, 0.53-1.34), low birth weight (LBW) (aRR, 0.92; 99.5% CI, 0.73-1.16), high birth weight (HBW) (aRR, 0.94; 99.5% CI, 0.75-1.18) and very-high birth weight (VHBW) (aRR, 1.05; 99.5% CI, 0.66-1.65). The risk of congenital anomaly was 16% higher in the blastocyst-stage group than in the cleavage-stage group, but this was not statistically significant (aRR, 1.16; 99.5% CI, 0.90-1.49). The chance of having a healthy baby (born at term, with a normal birth weight and no congenital anomalies) was not altered by extended culture (aRR, 1.00; 99.5% CI, 0.93-1.07). Extended culture was associated with a marginal increase in the chance having a male baby in the main cycle-based analysis (aRR, 1.04; 99.5% CI, 1.01-1.09) but not in the sub-group analysis of women undergoing their first cycle of treatment (aRR, 1.04; 95% CI, 1.00-1.08). In the sub-group analysis, the risk of congenital anomalies was significantly higher after blastocyst-stage embryo transfer (aRR, 1.42; 95% CI, 1.12-1.81).

Limitations, Reasons For Caution: This study is limited by the use of observational data and inability to adjust for key confounders, such as maternal smoking status and body mass index (BMI), which were not recorded in the HFEA dataset. As the main analysis was cycle-based and we were unable to link cycles within women undergoing more than one IVF/ICSI cycle, we undertook a sub-group analysis on women undergoing their first treatment cycle.

Wider Implications Of The Findings: Our findings should reassure women undergoing blastocyst-stage embryo transfer. For the first time, we have shown that babies born after blastocyst transfer have a similar chance of being healthy as those born after cleavage-stage embryos transfer.

Study Funding/competing Interest(s): The research activity of Dr Nicola Marconi was funded by the scholarship 'A. Griffini-J. Miglierina', Fondazione Comunitaria del Varesotto, Provincia di Varese, Italy. The authors do not have any competing interests to disclose.

Trial Registration Number: N/A.