A prospective, randomized trial on the effect of atmospheric versus reduced oxygen concentration on the outcome of intracytoplasmic sperm injection cycles. A controlled randomized trial evaluating the effect of lowered incubator oxygen tension on live births in a predominantly blastocyst transfer program. Low-oxygen compared with high-oxygen atmosphere in blastocyst culture, a prospective randomized study.
To assess whether the embryo cultivation at different oxygen tensions had any effect on intracytoplasmic sperm injection (ICSI) outcome.
                Prospective randomized trial.
                University clinical center.
                Women undergoing ICSI (n = 647).
                Culturing of embryos, either at 6% CO(2), 5% O(2), 89% N(2), or at 6% CO(2) in air.
                The primary outcome was ongoing pregnancy rates (PR). Secondary outcomes: cumulative PRs, implantation, and embryo quality, for both treatment groups and clinical outcomes for subgroups (optimal cycles, poor responders, older women).
                Although low oxygen resulted in a higher proportion of good day 2 embryos (0.547 +/- 0.021 vs. 0.39 +/- 0.019) and optimal blastocysts (0.162 +/- 0.199 vs. 0.083 +/- 0.128), the ongoing PRs (31.6% vs. 27.1%) and implantation rates (28.8% vs. 25.2%) were similar in both oxygen groups. Low oxygen caused a higher cumulative PR (38% vs. 28.3%) in the main group and a higher PR in the poor responder subgroup (23% vs. 9.8%) with embryo transfers performed mostly on day 3.
                The use of reduced oxygen in IVF is reasonable, irrespective of the duration of embryo culture. It improves embryo development and cumulative PR and is also recommended in poor responding cycles.
                Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved. The potentially damaging effect of free O(2) radicals to cultured embryos may be reduced by adding scavengers to the culture media or by reducing the incubator O(2) levels. However, lowering the O(2) in the culture environment can be expensive, troublesome and may not be justifiable. The objective of this study was to evaluate the effect of lowered incubator O(2) tension on live birth rates in a predominately Day 5 embryo transfer program.
                Two hundred and thirty first-cycle women undergoing routine IVF or ICSI with ejaculated sperm were randomized in a prospective clinical trial and stratified for patient age and physician. Embryos of patients were randomly assigned for culture in either a 21% O(2) (atmospheric) or 5% O(2) (reduced) environment. Clinical endpoints monitored were rates of implantation, clinical pregnancy, live birth and blastocyst cryopreservation.
                Embryos cultured in a 5% O(2) environment consistently resulted in higher rates of live birth implantation (106/247, 42.9% versus 82/267, 30.7%; difference of 12.2% with 95% confidence interval (CI) of 3.9-20.3, P = 0.005) and live births (66/115, 57.4% versus 49/115, 42.6%; difference of 14.8% with 95% CI of 1.9-27.0, P = 0.043) when compared with rates among women whose embryos were cultured in an atmospheric O(2) environment.
                The overall increase in live births demonstrated by this study indicates that the effort and expense to culture embryos in a low-O(2) environment is justified. The study was registered at clinicaltrials.gov. NCT00708487. To investigate birth rates with two oxygen (O(2)) concentrations in blastocyst culture.
                Randomized trial.
                Private in vitro fertilization (IVF) clinic.
                Six hundred women undergoing IVF.
                Blastocyst culture in atmospheres with either 6% carbon dioxide (CO(2)) in air, the equivalent to 19% O(2), a two-gas system; or 5% O(2), 6% CO(2), and 90% nitrogen (N(2)), a three-gas system.
                Birth rate.
                The inclusion criterion for blastocyst culture (at least five fertilized oocytes) was fulfilled in 396 women, randomized to 197 cultures with the three-gas system and 199 cultures with the two-gas system. The outcome with the three-gas system compared with the two-gas system showed a statistically significantly increased blastocyst rate (47.8% vs. 42.1%), mean number of blastocysts (3.8 vs. 3.3), and number of cryopreserved blastocysts (1.7 vs. 1.1). The mean number of transferred blastocysts was 1.2 versus 1.3. Culture with the three-gas system increased the relative birth rate by 10% compared with the two-gas system (42% vs. 32%, respectively), a statistically significant difference. The overall twin rate was 4.8%.
                Blastocyst culture with low-oxygen (5%) versus high-oxygen (19%) concentration yielded a better blastocyst outcome and a marked improvement in birth rate. Generation of cytotoxic reactive oxygen species with prolonged embryo culture might deteriorate blastocyst viability.
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.