Effect of oxygen concentration on human in-vitro fertilization and embryo culture

Abstract

In this prospective randomized study on 1380 consecutive in-vitro fertilization (IVF) treatments, the results were compared of culture of human oocytes and embryos for the first 2 or 3 days of development in microdroplets of medium under oil using a gas phase containing either atmospheric (approximately 20%) or reduced (5%) O2 concentrations. No significant differences were found between the two groups cultured under either 5% or 20% O2 in rates of fertilization (60 versus 61%, respectively), embryo development at day 2 or 3, pregnancy (26.6 versus 25.4%, respectively), and implantation (13.4 versus 14.0%, respectively). Culture of surplus embryos under 5% O2 resulted in a significantly higher mean incidence of blastocyst formation per cycle as compared to the 20% O2 group (25.8 +/- 2.0 versus 20.4 +/- 1.9, respectively). The mean number of cells of embryos classified as blastocysts by microscopic observation of a blastocoel was significantly higher in the 5% O2 group as compared to the 20% O2 group, both in blastocysts fixed on day 5 (39.8 +/- 1.7 versus 31.9 +/- 1.9, respectively), as well as those fixed on day 6 (45.6 +/- 2.6 versus 33.7 +/- 3.4, respectively). This difference was due to the fact that significantly more blastocysts of the 20% O2 group had an abnormal low cell number of < 25 as compared to the 5% O2 group, both in blastocysts fixed on day 5 (39 versus 22%, respectively), as well as those fixed on day 6 (43 versus 22%, respectively). To conclude, although culture under 5% O2 leads to slightly improved preimplantation embryonic viability, this effect is either too marginal to result in higher pregnancy rates, or low O2 concentrations exert an effect during the later stages of preimplantation development only.

The effect of two distinct levels of oxygen concentration on embryo development in a sibling oocyte study

“…No significant differences were found in fertilization, cleavage, pregnancy and implantation rates during the culture of embryos up to day 2 or day 3 when using O 2 concentrations of 5 % or 20 % [7]. On the other hand, significantly more surplus embryos reached the blastocyst stage when cultured under 5 % O 2 compared to 20 % O 2 concentration and had more cells when fixed on day 5 as well as on day 6 [6]. A better blastocyst outcome and a significant improvement in pregnancy and birth rates were found with low oxygen concentrations by Waldenström et al [27], but their study was not conducted on sibling oocytes.…”

“…Dumoulin et al [6,7] showed that the 5 % concentration level had no advantage over the 20 % oxygen concentration level with respect to fertilization, cleavage, pregnancy and implantation rates, but that it did improve the blastulation rate and the mean number of cells in blastocysts on day 5 and day 6. Gardner and Lane [10] also showed a 62 % blastulation rate for the lower concentration compared with 30 % for the higher one.…”

Effects of oxygen tension and IGF-I on HIF-1α protein expression in mouse blastocysts

“…Oxygen tension has been known to influence embryo development and cell numbers in a number of species, and improvements in embryo development have been observed under lower oxygen tensions (5 % or 7 %) rather than under an atmospheric oxygen condition (20 %) [23][24][25][26]. Several reports suggested that mouse and bovine embryos have the capacity to detect and respond to low oxygen environment with changes in the expression of oxygen-regulated genes such as glucose transporter-1 (GLUT-1), GLUT-3, and vascular endothelial growth factor (VEGF) [7][8][9]27].…”

“…Therefore, IGF-I may promote embryonic development by an anti-apoptotic effect instead of increasing HIF-1α expression. Embryos cultured in vitro under low (5 %) oxygen tension have been reported to show higher developmental rates than those cultured under 20 % oxygen in mice [43], cattle [44], and human [23]. These reports indicated that a high oxygen tension during in vitro culture was found to be toxic to mammalian embryos, probably due to the formation of reactive oxygen species (ROS) [45,46].…”

Diploid, but not haploid, human embryonic stem cells can be derived from microsurgically repaired tripronuclear human zygotes

“…21 Therefore, some studies suggested that the viability of pre-implantation embryos and the quality of blastocysts were all improved significantly when the embryos were cultured under conditions of low oxygen concentration. 22,23 More importantly, Lengner et al demonstrated that the human blastocysts contained pre-X-inactivation cells, and that this state was preserved in vitro through culture under 5% oxygen, which suggested that not only blastocyst formation but also ES cell derivation from these blastocysts was improved under hypoxic conditions. 24 Therefore, the hypoxic conditions would contribute to the improvement of the developmental competence of embryos and should be tested in the culture process of r1PN embryos in further study.…”