The impact of selected embryo culture conditions on ART treatment cycle outcomes: a UK national study

Abstract

Study question: Are selected embryo culture conditions namely media, oxygen level, and incubator type, associated with IVF live birth rate (LBR) and the health of singleton offspring at birth?

Summary answer: There were statistically significant differences in LBR between the eight culture media systems analysed; however, none of the embryo culture factors showed statistically significant associations with birth weight (BW) in multivariable regression analyses.

What is known already: In clinical ART culture media is the initial environment provided for the growth of human embryos. Pre-implantation development is a critical period of developmental plasticity, which could have long-lasting effects on offspring growth and health. Although some studies have shown an impact of culture medium type on BW, the interaction between culture medium type and associated culture conditions on both treatment success rates (LBR) and offspring BW is largely unexplored. This study aimed to examine these factors in a large multicentre national survey capturing the range of clinical practice.

Study design size duration: In this cross-sectional study, data from a survey circulated to all UK IVF clinics requesting information regarding culture medium type, incubator type, and oxygen level used in ART between January 2011 and December 2013 were merged with routinely recorded treatment and outcome data held in the Human Fertilisation and Embryology Authority Register up to the end of 2014.

Participants/materials setting methods: Forty-six (62%) UK clinics responded to the survey. A total of 75 287 fresh IVF/ICSI cycles were captured, including 18 693 singleton live births. IVF success (live birth, singleton or multiple; LB), singleton gestation and singleton gestation-adjusted BW were analysed using logistic and linear regression models adjusting for patient/treatment characteristics and clinic-specific effects.

Main results and the role of chance: Culture medium type was shown to have some impact on LBR (multivariable logistic regression, (MRL); post-regression Wald test, P < 0.001), but not on BW (MLR; post-regression Wald test, P = 0.215). However, blastocyst culture had the largest observed effect on odds of LBR (odds ratio (OR) = 1.35, CI: 1.29-1.42), increased the risk of pre-term birth even when controlling for oxygen tension (MLR; OR = 1.42, CI: 1.23-1.63), and gestation-adjusted BW (MLR, β = 38.97 g, CI: 19.42-58.53 g) when compared to cleavage-stage embryo culture. We noted a very strong effect of clinic site on both LBR and BW, thus confounding between treatment practices and clinic site may have masked the effect of culture conditions.

Limitations reasons for caution: Larger datasets with more inter-centre variation are also needed, with key embryo culture variables comprehensively recorded in national treatment registries.

Wider implications of the findings: This study is the largest investigation of laboratory environmental effects in IVF on both LBR and singleton BW. Our findings largely agree with the literature, which has failed to show a consistent advantage of one culture media type over another. However, we noted some association of LBR with medium type, and the duration of embryo exposure to laboratory conditions (blastocyst culture) was associated with both LBR and singleton health at birth. Because of the strong effect of clinic site noted, further randomized controlled trials are needed in order to reliably determine the effect of embryo culture on IVF success rates and the growth and health of subsequent offspring.

Study funding/competing interests: This study was funded by the EU FP7 project grant EpiHealthNet (FP7-PEOPLE-2012-ITN -317 146). The authors have no competing interests to declare.

Keywords: ART; ICSI; assisted reproduction; birth weight; blastocyst embryo culture; culture media; developmental origins of health and disease; fertilization in vitro; live birth rate; pre-term birth.