Oxygen Tension on Human Embryonic Development

NCT ID: NCT03964805

Last Updated: 2019-05-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

773 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-09-01

Study Completion Date

2018-12-01

Brief Summary

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In mammals, uterine environment is at low oxygen concentration (2-8% O2). Thus, human embryo culture under low O2 tension (5%) is now recommended by European Society of Human Reproduction and Embryology (ESHRE) revised guidelines for good practices in in vitro fertilization (IVF) labs. Indeed, hypoxia seems to improve embryo quality at cleavage and blastocyst stages, presumably by reducing damages of oxidative stress (OS). Nevertheless, recent meta-analyses concluded only with a low evidence to a superiority of hypoxia on IVF/ICSI outcomes. Furthermore, a study on mouse embryos suggested a negative impact of OS only at cleavage stage. The aim of the present prospective randomized study was to investigate this hypothesis for the first time in human embryos.

Detailed Description

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In mammals, uterine environment is at low oxygen tension, between 2 and 8% O2 . However, most IVF labs perform embryo culture at atmospheric tension (around 20% O2). Several randomized studies in human embryos have reported the superiority of hypoxia (5%) in terms of embryo quality and blastulation rates. This fact might be explained by a more physiological environment, probably inducing a decrease in oxidative stress (OS), which has a harmful impact on embryo development. Other studies have also suggested that before compaction, OS damages might be irreversible.

Wale et Gardner have investigated this impact of oxygen tension on mouse embryo development, by comparing four culture conditions: (i) group 1: culture exclusively at 5% O2 ; (ii) group 2: culture at 5% from Day 0 to Day 2, then at 20% from Day 2 to Day 4; (iii) group 3: at 20% then at 5% from Day 2; (iv) and group 4: culture exclusively at 20% Interestingly, no difference in terms of blastulation had been reported between groups 1 and 2, suggesting the OS might impact only at cleavage stage, and that switching culture under atmospheric conditions from Day 2/3 might not influence embryo development thereafter.

Hence, all those investigations suggest that embryo culture using trigas incubators (5% O2, 6% CO2 and 89% N2) would be preferable. However, this system is very expensive, notably due to a high N2 consumption, and requires a more complicated logistics (e.g. N2 levels monitoring). Yet, Wale and Gardner's results imply that sequential culture conditions (trigas from Day 0 to Day 2/3, then conventional incubator at 20% O2 until blastocyst stage) could be an valuable option, reducing the costs and, essentially, without any detrimental impact on embryo development.

The present study has two main objectives: (i) to confirm the improvement in embryo quality under low oxygen tension and (ii) to demonstrate the negative impact of OS only at cleavage stage in human embryos, as assumed by Wale and Gardner. For that purpose, we designed an original prospective randomized study comparing three culture conditions: (i) culture excusively at 20% O2 (Day 0 to Day 6) (Group A); (ii) culture exclusively at 5% O2 (Day 0 to Day 6) (Group B); (iii) culture at 5% from Day 0 to Day 3, then at 20% from Day 3 to Day 6) (Group C). Inclusion criteria and outcome measures are detailed in the following sections.

Conditions

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Infertility Embryo Culture Hypoxia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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group A

Embryo culture at 20% O2

Group Type ACTIVE_COMPARATOR

20% oxygen

Intervention Type OTHER

culture excusively at 20% O2 (Day 0 to Day 6)

group B

Embryo culture at 5% O2

Group Type ACTIVE_COMPARATOR

5% oxygen

Intervention Type OTHER

culture excusively at 5% O2 (Day 0 to Day 6)

group C

Embryo culture at 5% O2 and at 20% O2

Group Type ACTIVE_COMPARATOR

20 % and 5 % oxygen

Intervention Type OTHER

culture at 5% from Day 0 to Day 3, then at 20% from Day 3 to Day 6)

Interventions

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20% oxygen

culture excusively at 20% O2 (Day 0 to Day 6)

Intervention Type OTHER

5% oxygen

culture excusively at 5% O2 (Day 0 to Day 6)

Intervention Type OTHER

20 % and 5 % oxygen

culture at 5% from Day 0 to Day 3, then at 20% from Day 3 to Day 6)

Intervention Type OTHER

Other Intervention Names

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culture at 20% O2 culture at 5% O2 culture at 20 % and at 5%O2

Eligibility Criteria

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Inclusion Criteria

* Age: 18 - 39 years
* IVF / ICSI Attempt with Ejaculated Sperm Sperm (Fresh or Frozen)
* At least 8 oocytes retrieved in total
* Good understanding of the protocol by the patient
* Informed and consentment signed of the couple

Exclusion Criteria

* \- Hydrosalpinx
Minimum Eligible Age

18 Years

Maximum Eligible Age

39 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Christophe Sifer

Role: PRINCIPAL_INVESTIGATOR

AP-HP_Hôpital Jean Verdier

References

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Ciray HN, Aksoy T, Yaramanci K, Karayaka I, Bahceci M. In vitro culture under physiologic oxygen concentration improves blastocyst yield and quality: a prospective randomized survey on sibling oocytes. Fertil Steril. 2009 Apr;91(4 Suppl):1459-61. doi: 10.1016/j.fertnstert.2008.07.1707. Epub 2008 Aug 22.

Reference Type BACKGROUND
PMID: 18722608 (View on PubMed)

Fischer B, Bavister BD. Oxygen tension in the oviduct and uterus of rhesus monkeys, hamsters and rabbits. J Reprod Fertil. 1993 Nov;99(2):673-9. doi: 10.1530/jrf.0.0990673.

Reference Type BACKGROUND
PMID: 8107053 (View on PubMed)

Guo N, Li Y, Ai J, Gu L, Chen W, Liu Q. Two different concentrations of oxygen for culturing precompaction stage embryos on human embryo development competence: a prospective randomized sibling-oocyte study. Int J Clin Exp Pathol. 2014 Aug 15;7(9):6191-8. eCollection 2014.

Reference Type BACKGROUND
PMID: 25337269 (View on PubMed)

Kasterstein E, Strassburger D, Komarovsky D, Bern O, Komsky A, Raziel A, Friedler S, Ron-El R. The effect of two distinct levels of oxygen concentration on embryo development in a sibling oocyte study. J Assist Reprod Genet. 2013 Aug;30(8):1073-9. doi: 10.1007/s10815-013-0032-z. Epub 2013 Jul 9.

Reference Type BACKGROUND
PMID: 23835722 (View on PubMed)

Kea B, Gebhardt J, Watt J, Westphal LM, Lathi RB, Milki AA, Behr B. Effect of reduced oxygen concentrations on the outcome of in vitro fertilization. Fertil Steril. 2007 Jan;87(1):213-6. doi: 10.1016/j.fertnstert.2006.05.066. Epub 2006 Nov 1.

Reference Type BACKGROUND
PMID: 17081523 (View on PubMed)

Kirkegaard K, Hindkjaer JJ, Ingerslev HJ. Effect of oxygen concentration on human embryo development evaluated by time-lapse monitoring. Fertil Steril. 2013 Mar 1;99(3):738-744.e4. doi: 10.1016/j.fertnstert.2012.11.028. Epub 2012 Dec 11.

Reference Type BACKGROUND
PMID: 23245683 (View on PubMed)

Kovacic B, Vlaisavljevic V. Influence of atmospheric versus reduced oxygen concentration on development of human blastocysts in vitro: a prospective study on sibling oocytes. Reprod Biomed Online. 2008 Aug;17(2):229-36. doi: 10.1016/s1472-6483(10)60199-x.

Reference Type BACKGROUND
PMID: 18681997 (View on PubMed)

Waldenstrom U, Engstrom AB, Hellberg D, Nilsson S. Low-oxygen compared with high-oxygen atmosphere in blastocyst culture, a prospective randomized study. Fertil Steril. 2009 Jun;91(6):2461-5. doi: 10.1016/j.fertnstert.2008.03.051. Epub 2008 Jun 12.

Reference Type BACKGROUND
PMID: 18554591 (View on PubMed)

Wale PL, Gardner DK. Time-lapse analysis of mouse embryo development in oxygen gradients. Reprod Biomed Online. 2010 Sep;21(3):402-10. doi: 10.1016/j.rbmo.2010.04.028. Epub 2010 Aug 5.

Reference Type BACKGROUND
PMID: 20691637 (View on PubMed)

Wale PL, Gardner DK. The effects of chemical and physical factors on mammalian embryo culture and their importance for the practice of assisted human reproduction. Hum Reprod Update. 2016 Jan-Feb;22(1):2-22. doi: 10.1093/humupd/dmv034. Epub 2015 Jul 22.

Reference Type BACKGROUND
PMID: 26207016 (View on PubMed)

Other Identifiers

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2015-A02019-40

Identifier Type: -

Identifier Source: org_study_id

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