A controlled randomized trial evaluating the effect of lowered incubator oxygen tension on live births in a predominantly blastocyst transfer program

Meintjes, M.; Chantilis, S.J.; Douglas, James; Rodríguez, A.; Guerami, A.; Bookout, D.M.; Barnett, B.D.; Madden, James D.

doi:10.1093/humrep/den368

Cited by 155 publications

(108 citation statements)

References 28 publications

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“…All of them were prospective, but the randomization methods they used for examining the differences between the two oxygen concentrations from fertilization to ongoing pregnancies and live births are problematic. Randomization was either based on day of admission to the IVF laboratory [1], age of the woman, infertility factor, amount of gonadotrophins, number of retrieved oocytes [17], or per patient [15,19,27]. They all saw higher implantation, pregnancy and birth rates with reduced O 2 concentrations.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, a Cochrane review [3], based on three studies that are cited in the current study [16,19,27], found evidence of a beneficial effect of culturing in low oxygen concentrations for the 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.…”

Section: Discussionmentioning

confidence: 99%

“…Ciray et al's study [5] on sibling oocytes concluded that 5 % O 2 significantly improved the total blastocyst yield as well as the quality of day 3 and day 5 embryos. Finally, Meintjes et al's [19] study showed an overall increase in live births when embryos were cultured in reduced oxygen concentrations. A recent meta-analysis on four studies with a relatively low methodological quality showed a beneficial effect of culturing in low oxygen concentrations for live birth rates (OR 1.39; 95 % CI 1.11 to 1.76; P=0.005; I(2) = 0 %).…”

Section: Introductionmentioning

confidence: 97%

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

Kasterstein

Strassburger

Komarovsky

et al. 2013

J Assist Reprod Genet

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Purpose This prospective randomized study used sibling oocytes of 258 women with ≥8 oocytes to compare the effect of 5 % O 2 versus 20 % O 2 concentrations on embryo development and clinical outcome. Methods Oocytes of each case were divided between incubators with either 5 % or 20 % O 2 concentration. Outcome measures were fertilization, cleavage, embryo quality, blastocyst formation, and implantation, pregnancy and live birth rates. Results Fertilization and cleavage rates were similar in both groups. The 5 % O 2 group had significantly more blastomeres (P<0.05) and more top-quality embryos on day 3 (P<0.02), as well as significantly more available embryos for transfer (31.6 % vs. 23.1 % for the 20 % O 2 group; P<0.0001). There were significantly more cycles with good embryos in the 5 % group (76/258) than in the 20 % group (38/258) (P<0.0001). Implantation and pregnancy rates were significantly higher for 5 % O 2 embryos (P<0.03 and P<0.05, respectively). Live birth rates per embryo transfer were 34.2 % and 15.8 %, respectively, P<0.05. Conclusions Implantation, pregnancy and live birth rates are higher, and more good quality embryos are available for transfer and freezing with reduced rather than with atmospheric oxygen concentrations during embryo incubation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

See 1 more Smart Citation

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

Kasterstein

Strassburger

Komarovsky

et al. 2013

J Assist Reprod Genet

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“…Our second model of environmental stress examined the effect of incubator oxygen tension on mRNA abundance and stability. Mouse studies have shown for some years (Harlow & Quinn 1979), but more recently human studies have also shown improved developmental and pregnancy rates (Kovacic & Vlaisavljević 2008, Meintjes et al 2009, Waldenström et al 2009) when cultured under a lower oxygen tension (5%) than conventionally used (20%). Furthermore, high oxygen tension greatly increases the number of genes aberrantly expressed in the mouse embryo (Rinaudo et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Culture medium, gas atmosphere and MAPK inhibition affect regulation of RNA-binding protein targets during mouse preimplantation development

Calder¹,

Watson²,

Watson³

2011

Reproduction

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During oogenesis, mammalian oocytes accumulate maternal mRNAs that support the embryo until embryonic genome activation. RNA-binding proteins (RBP) may regulate the stability and turnover of maternal and embryonic mRNAs. We hypothesised that varying embryo culture conditions, such as culture medium, oxygen tension and MAPK inhibition, affects regulation of RBPs and their targets during preimplantation development. STAU1, ELAVL1, KHSRP and ZFP36 proteins and mRNAs were detected throughout mouse preimplantation development, whereas Elavl2 mRNA decreased after the two-cell stage. Potential target mRNAs of RBP regulation, Gclc, Slc2a1 and Slc7a1 were detected during mouse preimplantation development. Gclc mRNA was significantly elevated in embryos cultured in Whitten's medium compared with embryos cultured in KSOMaa, and Gclc mRNA was elevated under high-oxygen conditions. Inhibition of the p38 MAPK pathway reduced Slc7a1 mRNA expression while inhibition of ERK increased Slc2a1 mRNA expression. The half-lives of the potential RBP mRNA targets are not regulated in parallel; Slc2a1 mRNA displayed the longest half-life. Our results indicate that mRNAs and proteins encoding five RBPs are present during preimplantation development and more importantly, demonstrate that expression of RBP target mRNAs are regulated by culture medium, gas atmosphere and MAPK pathways.

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“…Various factors, such as the culture medium characteristics [2,4,41], the laboratory conditions [23,27,46], the oocyte quality [6,18], and the sperm origin [32], may be responsible for this variation in the rate of blastocyst formation. However, the influence of the patient and cycle characteristics on blastocyst formation is not understood.…”

Section: Introductionmentioning

confidence: 99%

Patient selection criteria for blastocyst transfers in extended embryo culture programs

Braga

Setti

Figueira

et al. 2012

J Assist Reprod Genet

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Purpose To identify the correlation between different cycles, patient factors and blastocyst characteristics. Methods The study included 420 patients undergoing ICSI cycles and 2781 graded blastocysts, which took into account the blastocyst quality. The correlations between the blastocyst parameters and the patient and cycle characteristics were assessed. Results The blastocyst development was negatively correlated with the maternal age, BMI and dose of FSH. The ICM was negatively correlated with the FSH dose, whereas the TE quality was influenced by the FSH dose, the maternal age and the number of retrieved oocytes. The embryo morphology on days two and three may predict the blastocyst developmental competence. Conclusions Older patients and patients with high BMI should not be included in extended embryo culture programmes. The extended culture may not favour embryos with poor morphology on days two and three of development. Additionally, a lower ovarian stimulation and decreased oocyte yields may lead to the development of high-quality blastocysts.

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A controlled randomized trial evaluating the effect of lowered incubator oxygen tension on live births in a predominantly blastocyst transfer program

Abstract: 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.

Cited by 155 publications

References 28 publications

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

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

Culture medium, gas atmosphere and MAPK inhibition affect regulation of RNA-binding protein targets during mouse preimplantation development

Patient selection criteria for blastocyst transfers in extended embryo culture programs

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