Low oxygen concentrations for embryo culture in assisted reproductive technologies.
BACKGROUND
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.


OBJECTIVE
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.


METHODS
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.


METHODS
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.


METHODS
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.


RESULTS
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; I(2) = 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.


CONCLUSIONS
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.
Centre for Reproductive Medicine, Department of Obstetrics and Gynaecology, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands. stephanbontekoe@hotmail.com.
Stephan
S
Bontekoe
Eleni
E
Mantikou
Madelon
M
van Wely
Srividya
S
Seshadri
Sjoerd
S
Repping
Sebastiaan
S
Mastenbroek
D001755:Blastocyst; D046149:Embryo Culture Techniques / Q000379:methods*; D047108:Embryonic Development; D005260:Female; D006801:Humans; D050498:Live Birth / Q000453:epidemiology; D010100:Oxygen / Q000008:administration & dosage*; D011247:Pregnancy; D018873:Pregnancy Rate; D016032:Randomized Controlled Trials as Topic; D027724:Reproductive Techniques, Assisted
D010100:Oxygen