O-216 Culture medium used in IVF-treatment impacts post-implantation embryonic growth and developmental trajectories in a sex-specific manner
Authors: Van Duijn L , Steegers-Theunissen R , Baart E , Willemsen S , Laven J , Rousian M 
Published: August 2021

Abstract

Study question
What is the (sex-specific) impact of two different culture media used in in vitro fertilization (IVF) treatment on post-implantation growth and development?

Summary answer
Embryos, especially males, cultured in SAGE 1-Step grow and morphologically develop faster in the first trimester, when compared to those cultured in Vitrolife G-1 PLUS.

What is known already
Increasing success rates after IVF can be attributed to several advancements, such as improved culture conditions. Culture media are of special interest, as they supply the embryo with essential nutrients and have previously been shown to impact birthweight. Moreover, IVF pregnancies are associated with an increased male:female ratio. However, it is unknown if culture media also have an impact prenatally. Therefore, our aim is to study the (sex-specific) impact of two different culture media (SAGE 1-Step and Vitrolife G-1 PLUS) used in IVF treatment on first-trimester embryonic growth and development, and fetal outcomes.

Study design, size, duration
Women with a viable singleton pregnancy were included before 10 weeks of gestation in the Rotterdam Periconception Cohort, an ongoing prospective tertiary hospital-based study, conducted since November 2009.

Participants/materials, setting, methods
A total of 879 pregnancies were included; 153 after culture in Vitrolife G-1 PLUS, 251 after culture in SAGE 1-Step and 475 naturally conceived. First-trimester growth and development, defined by serial crown-rump length (CRL), embryonic volume (EV) and Carnegie stages measurements were performed using state-of-the-art imaging techniques. Secondary outcomes included second trimester estimated fetal weight (EFW) and birth outcomes, and were retrieved from medical records.

Main results and the role of chance
Linear mixed model analyses, adjusted for gestational age and maternal characteristics, showed that embryos cultured in SAGE 1-Step grow faster than those cultured in Vitrolife G-1 PLUS (βEV 0.030 ∛cm3 (95%CI 0.008-0.052), p=0.007). CRL and Carnegie stages were not statistically different between culture media. After stratification for fetal sex, similar results were observed for male embryos (βEV 0.048 ∛cm3 (95%CI 0.015-0.081), p=0.005), but not for female embryos. EFW and birth outcomes were comparable between culture media in the total population and after stratification for fetal sex. Embryos cultured in SAGE 1-Step also grow faster than those conceived naturally (βEV 0.033 ∛cm3 (95%CI 0.006-0.060), p=0.018). This association was also most pronounced in male embryos (βEV 0.066 ∛cm3 (95%CI 0.024-0.108), p=0.002).

Limitations, reasons for caution
Although this study has a prospective design, its observational character does not exclude residual confounding. Furthermore, the external validity of this explorative study is limited, since participants were recruited from a tertiary university hospital.

Wider implications of the findings
Culture in SAGE 1-Step culture medium is associated with faster first-trimester growth and development, especially in male embryos. This may be the result of altered susceptibility to preimplantation environmental stressors. Further research should focus on the (sex-specific) impact of culture media on postnatal development and the susceptibility to non-communicable diseases.

Trial registration number
N/A