Oxygen Tension on Human Embryonic Development

NCT03964805 | Completed

• 1 other identifier: 2015-A02019-40
• Study Type: interventional
• Target: 773
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Infertility; Embryo Culture; Hypoxia

Keywords

Embryo culture; oxygen tension,; embryo quality,; extended culture

Outcome Measures

Primary Outcomes (4)

• Embryo quality at Day 2 between groups A and B.

  Embryo morphology is qualified as the number of blastomeres, degree of cytoplasmic fragmentation, regularity of the cells and presence/absence of multinucleated blastomeres. Day 2 top-quality embryos are defined as 4 regular blastomeres, \<20% cytoplasmic fragmentation, no multinucleations.mbryos are defined as 4/8 regular blastomeres, \<20% cytoplasmic fragmentation, no multinucleations.

  Day 2

• Embryo quality at Day 3 between groups A and B.

  Embryo morphology is qualified as the number of blastomeres, degree of cytoplasmic fragmentation, regularity of the cells and presence/absence of multinucleated blastomeres. Day 3 top-quality embryos are defined as 8 regular blastomeres, \<20% cytoplasmic fragmentation, no multinucleations.

  Day 3

• Embryo quality at blastocyst stage (Day 5) between groups A, B and C.

  Blastocyst morphology is assessed according to Gardner and Schoolcraft's classification: degree of blastocele expansion (graded from B1 to B6), inner cell mass and trophectoderm morphology (both graded A, B or C). Day 5 top quality blastocyst are defined as ≥B4AA/AB/BA.

  Day 5

• Embryo quality at blastocyst stage (Day 6) between groups A, B and C.

  Blastocyst morphology is assessed according to Gardner and Schoolcraft's classification: degree of blastocele expansion (graded from B1 to B6), inner cell mass and trophectoderm morphology (both graded A, B or C). Day 5 top quality blastocyst are defined as ≥B4AA/AB/BA.

  Day 6

Secondary Outcomes (6)

• Fertilization rate

  Days 1

• Early cleavage rate

  25 hours after insemination

• Useable embryo rate

  Days 2/3; 5/6

• Implantation rate

  4-5 weeks after transfer

• Clinical pregnancy rate

  4-5 weeks after transfer

Study Arms (3)

group A

ACTIVE COMPARATOR

Embryo culture at 20% O2

Other: 20% oxygen

group B

ACTIVE COMPARATOR

Embryo culture at 5% O2

Other: 5% oxygen

group C

ACTIVE COMPARATOR

Embryo culture at 5% O2 and at 20% O2

Other: 20 % and 5 % oxygen

Interventions

20% oxygen OTHER

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

Also known as: culture at 20% O2

group A

5% oxygen OTHER

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

Also known as: culture at 5% O2

group B

20 % and 5 % oxygen OTHER

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

Also known as: culture at 20 % and at 5%O2

group C

Eligibility Criteria

• Age: 18 Years - 39 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• \- Hydrosalpinx

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Related Publications (10)

• 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.

  PMID: 18722608 BACKGROUND

• 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.

  PMID: 8107053 BACKGROUND

• 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.

  PMID: 25337269 BACKGROUND

• 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.

  PMID: 23835722 BACKGROUND

• 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.

  PMID: 17081523 BACKGROUND

• 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.

  PMID: 23245683 BACKGROUND

• 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.

  PMID: 18681997 BACKGROUND

• 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.

  PMID: 18554591 BACKGROUND

• 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.

  PMID: 20691637 BACKGROUND

• 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.

  PMID: 26207016 BACKGROUND

MeSH Terms

Conditions

Infertility; Hypoxia

Interventions

Oxygen

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chalcogens; Elements; Inorganic Chemicals; Gases

Study Officials

• Christophe Sifer

  AP-HP_Hôpital Jean Verdier

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2019
• First Posted: May 28, 2019
• Study Start: September 1, 2016
• Primary Completion: September 6, 2018
• Study Completion: December 1, 2018
• Last Updated: May 28, 2019

Record last verified: 2019-04