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. Enhancement of outcome from intracytoplasmic sperm injection: does co-culture or assisted hatching improve implantation rates? A prospective randomized study: day 2 versus day 5 embryo transfer. One versus two embryo transfer after IVF and ICSI: a randomized study. A randomised control trial examining the effect of an antioxidant (Menevit) on pregnancy outcome during IVF-ICSI treatment. Elective cryopreservation of all pronucleate embryos in women at risk of ovarian hyperstimulation syndrome: efficiency and safety. Prospectively randomized controlled trial of PGS in IVF/ICSI patients with poor implantation.
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. In two separate prospectively randomized trials, intracytoplasmic sperm injection (ICSI) cycles were studied in a controlled manner to monitor the effects of either bovine oviductal epithelial cell co-culture (n = 119) or assisted hatching by zona drilling (n = 100). In the first study, immediately following ICSI, all eggs were placed directly either onto partial monolayers of bovine oviductal cells or into regular culture medium. Although the embryo developmental rate was apparently compromised in part by the presence of the co-culture cells, ultimately there were no significant differences in either the viable pregnancy rate (31.6% co-culture versus 29.0% control) or the embryonic implantation rate (11.4% co-culture versus 13.6% control). Assisted hatching also had no significant impact on ICSI cycle outcome in terms of either the viable pregnancy rate (30.0% assisted hatching versus 32.0% control) or the embryonic implantation rate (8.5% assisted hatching versus 13.5% control). However, in female patients aged > or = 35 years, assisted hatching appeared to convey a marginally significant benefit in terms of both the viable pregnancy rate (35.5% assisted hatching versus 11.1% control) and the embryonic implantation rate (10.3% assisted hatching versus 3.1% control). It seems that the overall improvement of ICSI cycle outcome cannot be achieved by the general application of either co-culture or assisted hatching. Nevertheless, it is possible that there remain specific patient groups that might benefit from selected use of either of these modalities. This randomized controlled study was performed in an unselected IVF/ICSI population to test the hypothesis that blastocyst transfers result in higher clinical pregnancy rates (CPR) per oocyte retrieval when compared with day 2 transfers.
                Blind randomization for transfer on day 2 (group 1) or day 5/6 (group 2) was performed before stimulation. Oocytes and embryos were cultured in sequential media in 5.5% CO(2), 5% O(2), 89.5% N(2) and 90% humidity. A maximum of two embryos was transferred.
                The two groups were similar for age, IVF indication, number of treatment cycles, rate of ICSI/IVF, number of fertilized oocytes and number of embryos transferred. The CPR/oocyte retrieval was comparable in group 1 (32%) and in group 2 (44%), while the CPR/embryo transfer was significantly higher (P < 0.01) in group 2 (60%) than in group 1 (35%). Similarly, the implantation rate per embryo transferred was significantly higher (P < 0.03) in group 2 (46%) than in group 1 (29%). The cryo-augmented delivery rate/oocyte retrieval was comparable in group 2 (36.3%) and in group 1 (28.6%).
                This randomized study in an unselected population showed a significantly higher CPR/embryo transfer and a tendency toward a higher CPR/oocyte retrieval in patients receiving blastocysts when compared with day 2 transfers. The main reason for adverse treatment outcome in assisted reproduction is the high rate of multiple pregnancies. The only strategy to avoid dizygotic twins is to transfer one embryo at a time.
                A total of 144 women, who had had at least four good quality embryos available after IVF/intracytoplasmic sperm injection (ICSI) and who had no more than one previous failed treatment cycle, were randomized to have either one or two embryos transferred. The treatment outcomes including those after frozen embryo transfer were compared between these groups.
                The clinical pregnancy rate per transfer was 32.4% in the one embryo transfer group and 47.1% in the two embryo transfer group, the difference being not significant. Eleven twin deliveries (n = 39) occurred in the two embryo transfer group and there was one pair of monozygotic twins in the one embryo transfer group. The cumulative pregnancy rate per patient after transfer of fresh and frozen embryos was 47.3% in the one embryo transfer group and 58.6% in the two embryo transfer group.
                Our results indicate that among women who have good quality embryos in their first IVF/ICSI, good treatment results can be achieved. They support the idea of changing embryo transfer policy towards one embryo transfer without any remarkable decrease in the success rate, while dizygotic twins can be avoided. Evidence has accumulated supporting the role of reactive oxygen species (ROS) in the pathogenesis of sperm dysfunction among men with infertility. Damage to sperm DNA by ROS can lead to failure of conception, miscarriage or potentially even childhood cancer. The objective of this study was to examine the effect of male antioxidant treatment on embryo quality and pregnancy outcome during in vitro fertilisation-intracytoplasmic sperm injection (IVF-ICSI) treatment.
                Sixty couples with severe male factor infertility were enrolled in a prospective randomised double-blind placebo-controlled trial. Male participants were randomly assigned to take either one capsule per day of the Menevit antioxidant or an identical in appearance placebo for three months prior to their partner's IVF cycle. The primary outcome was cleavage stage embryo quality and the secondary outcomes were oocyte fertilisation rate, pregnancy rates and treatment side-effects. Approval by the local Human Research Ethics Committee was obtained prior to the commencement of this study.
                The antioxidant group recorded a statistically significant improvement in viable pregnancy rate (38.5% of transferred embryos resulting in a viable fetus at 13 weeks gestation) compared to the control group (16% viable pregnancy). No significant changes in oocyte fertilisation rate or embryo quality were detected between the antioxidant and the placebo groups. Side-effects on the Menevit antioxidant were rare (8%) and mild in nature.
                The Menevit antioxidant appears to be a useful ancillary treatment that significantly improves pregnancy rates in couples undergoing IVF-ICSI treatment for severe male factor infertility. In a prospective randomized study, we analysed 125 patients at risk of ovarian hyperstimulation syndrome (OHSS), selected in the period between January 1996 and July 1997. All the patients had blood oestradiol concentration >/=1500 pg/ml on the day of human chorionic gonadotrophin (HCG) administration and >/=15 oocytes were collected. The patients were matched in two groups: group A, control group (n = 67), had fresh embryo transfers; group B (n = 58) had cryopreservation of all obtained pronucleate embryos. Pregnancy, live birth rates and the incidence of OHSS were compared between the two groups. There were no significant differences in terms of pregnancies per patient (46.3 versus 48.3%) and live birth rates (38. 8 versus 39.6%). No cases of OHSS occurred in group B, while four patients developed the syndrome in group A. The implantation rate was slightly but not significantly lower in group B (chi2 = 1.03). These results suggest that elective cryopreservation of all zygotes might prevent the risk of OHSS in patients undergoing IVF treatment. In contrast to what has been reported by other authors, our results show that the elective cryopreservation of zygotes does not affect pregnancy and live birth rates. This randomized, controlled trial verifies whether patients with recurrent failed implantation benefit from preimplantation genetic diagnosis for aneuploidy, as compared with conventional assisted reproduction treatment procedures. Two hundred patients with recurrent failed implantation were randomized into two groups. A total of 139 patients underwent ovarian stimulation, and preimplantation genetic screening was performed in 72 patients. Analysis of chromosomes X, Y, 13, 16, 18, 21 and 22 was carried out using fluorescence in-situ hybridization in blastomeres of day-3 cleavage-stage embryos in the study group. The primary endpoint was implantation rate. Secondary endpoints were embryonic morphology and chromosomal status, number of transferred embryos and clinical pregnancy rate. With regard to the implantation rate, there was no significant difference between the study group (21.4%) and the control group (25.3%). The number of embryos transferred was significantly lower in the study group, namely 1.4 (SD 1.0) versus 2.1 (SD 1.0) in the control group (P < 0.05). The clinical pregnancy rate was not significantly different between the groups (25.0% in the study group versus 40.3% in the control group). It can be concluded that preimplantation genetic screening does not increase the implantation rates after IVF-intracytoplasmic sperm injection in women with repeated implantation failure.
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.