Influence of embryo culture medium (G5 and HTF) on pregnancy and perinatal outcome after IVF: a multicenter RCT

Abstract

18 July 2010.

Epigenetics and Reproductive Medicine

“…Further studies are required on whether the use of different culture media can affect birthweight in humans and on the possible effects of extended embryo culture. In agreement with the opinion of others, 63 and in view of the findings from the first randomised controlled trial on the effects of culture media on pregnancy and perinatal outcome, 64 greater transparency is essential with respect to the composition of embryo culture media.…”

“… At least two disorders of genomic imprinting, BWS and SRS appear to be associated with ARTs, however the occurrence of these disorders is very rare. Evidence from a large number of animal studies reveals that ARTs including embryo culture, superovulation , in vitro maturation of oocytes, micromanipulation and embryo transfer have the potential to produce epigenetic changes that can cause dysfunction in the conceptus or placenta. A small number of human studies show that although ARTs, such as superovulation and cell culture, can induce epigenetic changes in the gametes and/or preimplantation embryo, the developmental effects of these changes and their involvement in disease process are currently unknown. Whether epigenetic disturbance is caused by ARTs or an epigenetic error in the gametes is unclear, but it is possible that in some cases assisted reproduction exacerbates pre‐existing defects in the gametes. Further studies are required on whether the use of different culture media can affect birthweight in humans and on the possible effects of extended embryo culture. In agreement with the opinion of others, and in view of the findings from the first randomised controlled trial on the effects of culture media on pregnancy and perinatal outcome, greater transparency is essential with respect to the composition of embryo culture media. There is evidence for epigenetic differences and gene expression changes in ART cohorts when compared with those naturally conceived, although genome‐wide studies are required to confirm this. Emerging data indicate that long‐term consequences of ARTs may include cardiovascular and metabolic disorders, which may be due to compromised placental function. More research is required to ascertain the impact of ARTs and infertility on epigenetic programming on the human conceptus and any short‐term and/or long‐term developmental consequences that follow. Based on the evidence presented in this paper there is no consensus on how to counsel patients regarding epigenetic consequences of assisted reproduction but this should be a priority consideration once further evidence becomes available. …”

“…The influence of media on pregnancy and perinatal outcome after IVF has also been considered in a randomised control trial, published in 2016 . This study compared outcomes after embryo culture in either G5 or human tubal fluid media and reported that birthweight was significantly lower in the G5 group while the clinical pregnancy rate was significantly higher.…”

Metabolite availability as a window to view the early embryo microenvironment in vivo

“…Curiously, these differences further increase following mating, suggesting that preimplantation embryos of these animals experience lower temperatures to reduce metabolic rates, which is consistent with the "quiet hypothesis" and should benefit embryo development. Could such physiologic variation explain why human embryos cultured in human tubal fluid in vitro show lower implantation rate and/or live birth rate than those cultured in a synthetic G5 medium (Kleijkers et al, 2015(Kleijkers et al, , 2016Mantikou et al, 2016)? further revealing what happens in the female tract (Kolle, 2012;Wang, Burton, Behringer, & Larina, 2015).…”

Reformatting the reproductive tract to accommodate the needs of human ARTs

“…Some remain within the realm of the biophysical, drawing upon advances in the field of microfluidics [4]. Others have stagnated as the discourse continues over single or sequential media [5,6], compositional variants, and their influence on gene expression patterns in media comparisons [7]. In the end, even the question of what stage to transfer-cleavage or blastocyst-lingers while properly executed RCTs loom in a background of mediocrity in terms of clinical decision making [8].…”