Couples who experience difficulty conceiving are commonly referred for assisted reproductive technologies such as in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) as a way to achieve pregnancy. Over 3.5 million babies have been born worldwide from IVF and ICSI procedures. One of the main focuses of research in reproductive medicine is to optimise the treatment success of IVF and ICSI procedures. One such area has focused on improving the in vitro environment to which human embryos are exposed before implantation into the uterus. An important component of this in vitro environment is the oxygen concentration. Traditionally, embryos have been cultured under atmospheric oxygen concentrations (~ 20%), probably because culturing at lower oxygen concentration requires additional expenses. More recently there has been a shift towards the use of lower oxygen concentrations (~ 5%) as these more closely resemble the oxygen concentration under natural conditions (2% to 8%). The results of clinical studies that have been undertaken to study the effect on the outcomes of IVF and ICSI procedures of culturing embryos under low oxygen concentrations have been conflicting. Therefore, we performed a systematic review and meta-analysis of the literature to find the best available evidence. It has shown that culturing embryos under low oxygen concentrations does indeed improve clinical outcomes after IVF and ICSI, such as number of deliveries (live birth rate) and ongoing and clinical pregnancy rates. Furthermore, no evidence was found of an increased risk of adverse events such as multiple pregnancies, miscarriages and congenital abnormalities. We concluded that culturing embryos under low oxygen concentrations seems beneficial with an increase in the number of newborns, but more studies are needed to strongly prove this effect.
The results of this systematic review and meta-analysis suggest that culturing embryos under conditions with low oxygen concentrations improves the success rates of IVF and ICSI, resulting in the birth of more healthy newborns.
During in vitro fertilisation (IVF) procedures, human preimplantation embryos are cultured in the laboratory. While some laboratories culture in an atmospheric oxygen concentration (~ 20%), others use a lower concentration (~ 5%) as this is more comparable to the oxygen concentration observed in the oviduct and the uterus. Animal studies have shown that high oxygen concentration could have a negative impact on embryo quality via reactive oxygen species causing oxidative stress. In humans, it is currently unknown which oxygen concentration provides the best success rates of IVF procedures, eventually resulting in the hightest birth rate of healthy newborns.
To determine whether embryo culture at low oxygen concentrations improves treatment outcome (better embryo development and more pregnancies and live births) in IVF and intracytoplasmic sperm injection (ICSI) as compared to embryo culture at atmospheric oxygen concentrations.
The Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and PsycINFO electronic databases were searched (up to 4th November 2011) for randomised controlled trials on the effect of low oxygen concentrations for human embryo culture. Furthermore, reference lists of all obtained studies were checked and conference abstracts handsearched.
Only truly randomised controlled trials comparing embryo culture at low oxygen concentrations (~ 5%) with embryo culture at atmospheric oxygen concentrations (~ 20%) were included in this systematic review and meta-analysis.
Two review authors selected the trials for inclusion according to the above criteria. After that two authors independently extracted the data for subsequent analysis, and one author functioned as a referee in case of ambiguities. The statistical analysis was performed in accordance with the guidelines developed by The Cochrane Collaboration.
Seven studies with a total of 2422 participants were included in this systematic review. Meta-analysis could be performed with the data of four included studies, with a total of 1382 participants. The methodological quality of the included trials was relatively low. Evidence of a beneficial effect of culturing in low oxygen concentration was found for live birth rate (OR 1.39; 95% CI 1.11 to 1.76; P = 0.005; I2 = 0%); this would mean that a typical clinic could improve a 30% live birth rate using atmospheric oxygen concentration to somewhere between 32% and 43% by using a low oxygen concentration. The results were very similar for ongoing and clinical pregnancy rates. There was no evidence that culturing embryos under low oxygen concentrations resulted in higher numbers of adverse events such as multiple pregnancies, miscarriages or congenital abnormalities.