P-256 Large for gestational age in singletons born following frozen embryo transfer: due to freezing technique or to endometrial preparation protocol? Lessons from the French registry
Authors: Sermondade N , Hesters L , Lambert C , Pouly J L , Pereira B , Lévy R , Brugnon F 
Published: June 2023

Abstract

Study question
Is large for gestational age (LGA) observed in singletons born following frozen embryo transfers (FET) either due to freezing technique or to endometrial preparation protocol?

Summary answer
Artificial cycles were associated with a higher rate of LGA when compared to ovulatory cycles, whereas no difference was observed between the freezing techniques.

What is known already
Several studies compared neonatal outcomes after fresh embryo transfer (fresh ET) and FET, and showed that FET was associated with improved neonatal outcomes, including reduced risks of preterm birth, low birth weight and small for gestational age (SGA) when compared to fresh ET. However, these studies also revealed an increased risk of LGA after FET. The underlying pathophysiology remains unclear; parental infertility, laboratory procedures including embryo culture conditions and freezing-thawing processes, as well as endometrial preparation treatments might be at play.

Study design, size, duration
A multicentric epidemiological data study was performed through a retrospective analysis of the standardized individual clinical records of the French national registry of in vitro fertilisation (IVF) from 2014 to 2018, including deliveries resulting from fresh ET and FET that were prospectively collected in fertility centres. Complementary data were collected from the participating fertility centres including the vitrification media and devices, as well as the endometrial preparation protocols.

Participants/materials, setting, methods
Data were collected from 35 French fertility centres, leading to the inclusion of a total of 72,789 fresh ET, 10,602 slow-freezing FET and 30,062 vitrification FET cycles. Fetal growth disorders were defined in liveborn singletons according to gestational age and sex-specific weight percentile distribution: SGA and LGA if &lt; 10th and &gt;90th percentile, respectively. Analyses were performed using linear mixed models with the centres as random effect.

Main results and the role of chance
Among a total of 26,585 liveborn singletons, 16,413 babies were born from fresh ET, 1,644 from slow-freezing FET and 8,528 from vitrification FET. Birthweight was significantly higher in the FET groups compared to the fresh ET group, with no difference between the two freezing techniques. Likewise, LGA rates were higher and SGA rates were lower in the FET groups compared to the fresh ET group (12.0% vs 6.4%, p &lt; 0.001, and 7.8% vs 13.4%, p &lt; 0.001 respectively). In a multivariable analysis, the risk of LGA following FET was not different between stimulated and natural cycles (adjusted odds ratio: 1.06, 95% confidence interval: 0.83-1.35, p = 0.64) but was significantly increased in artificial compared to natural cycles (aOR 1.36 [1.11-1.67], p = 0.003). On the contrary, the risk of LGA was not associated with either the freezing mode (slow-freezing vs vitrification) or the embryo stage (cleaved embryo vs blastocyst). When focusing on vitrification, the risk of LGA was not associated with either the freezing medium used or the embryo stage, and no difference was observed according to the vitrification device.

Limitations, reasons for caution
Most of the vitrification techniques were performed using the same device, and with two major vitrification media, limiting the interpretability of the comparison of the risk for LGA according to the device or the vitrification media.

Wider implications of the findings
Our results seem reassuring regarding potential fetal growth disorders following embryo vitrification in comparison to slow-freezing. Even if other factors may be involved, the impact of the endometrial preparation treatments seems to prevail for LGA risk following FET. FET during ovulatory cycles could minimize the risk for fetal growth disorders.

Trial registration number
N/A