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Influence of Manipulation of Oocytes and Embryos in Low Oxygen Tension on Assisted Reproduction Technology Outcome

Primary Purpose

Embryo Hypoxia

Status
Unknown status
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
5% O2
Sponsored by
The University of Hong Kong-Shenzhen Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Embryo Hypoxia

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • all the couples undergoing conventional IVF cycle in the reproductive medicine center of the University of Hong Kong-Shenzhen Hospital

Exclusion Criteria:

  • Intracytoplasmic sperm injection (ICSI) cycle
  • Preimplantation genetic testing (PGT) cycle
  • cycle with fertilization failure ≥3
  • cycle using sperm from percutaneous epididymal sperm aspiration (PESA)/testicular sperm extraction (TESE) or cryopreserved sperm
  • cycle using cryopreserved oocyte
  • cycle with no oocyte retrieved

Sites / Locations

  • Reproductive medicine centerRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

20% O2

5% O2

Arm Description

In the control group, oocyte pickup will be performed in atmospheric oxygen environment (20% oxygen, 89% nitrogen, 6% carbon dioxide).

In the experimental group, oocyte pickup will be performed in a low oxygen tension environment (5% oxygen, 89% nitrogen, 6% carbon dioxide). If time lapse embryo culture system is used, fertilization check and embryo grading will also be conducted under the low oxygen tension environment.

Outcomes

Primary Outcome Measures

live birth rate
delivery of a live birth beyond 24 weeks of gestation

Secondary Outcome Measures

clinical pregnancy rate
presence of at least one gestational sac on ultrasound of 6 weeks
ongoing pregnancy rate
presence of at least heart pulsation on ultrasound beyond 20 weeks
fertilization rate
No. of fertilized oocyte divided by No. of inseminated cumulus-oocyte complexes (COCs)
cleavage rate
No. of cleaved embryo divided by No. of fertilized oocyte

Full Information

First Posted
May 28, 2020
Last Updated
May 21, 2021
Sponsor
The University of Hong Kong-Shenzhen Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04424784
Brief Title
Influence of Manipulation of Oocytes and Embryos in Low Oxygen Tension on Assisted Reproduction Technology Outcome
Official Title
Influence of Manipulation of Oocytes and Embryos in Low Oxygen Tension on Assisted Reproduction Technology Outcome
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Unknown status
Study Start Date
March 22, 2021 (Actual)
Primary Completion Date
June 2023 (Anticipated)
Study Completion Date
June 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The University of Hong Kong-Shenzhen Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
Nowadays, most assisted reproduction laboratories attempt to maintain as much as possible ex vivo culture conditions comparable to those in vivo. Various culturing condition such as temperature and pH parameters have been adjusted according to in vivo values in order to improve in-vitro fertilization (IVF) outcomes. Embryos of most mammals, including that of humans, are not exposed to oxygen concentration higher than 8%. Thus, embryos and gametes should be kept in a low oxygen environment during manipulation in assisted reproduction treatment. Culturing embryos in low oxygen concentrations is now a general practice in IVF laboratories. However, there are still laboratory procedures when the oocytes/embryos are exposed to atmospheric oxygen. In most laboratories, oocytes retrieval is performed under atmospheric oxygen concentration. Oocyte is very sensitive to environmental changes, for instance, transient cooling to room temperature can cause irreversible disruption of the meiotic spindle in human oocytes and oocyte in vitro maturation can lead to the decline of energy metabolism in human oocytes. Whether oocyte exposed to atmospheric oxygen during oocyte retrieval has detrimental effect on embryo development and IVF outcomes is unknown. Previous studies showed that low oxygen tension during embryo culture improved implantation rate and clinical outcomes, but embryo quality was not affected. In other studies, embryo quality was improved but overall pregnancy was not affected. The reason for the discrepancies could be because the oxygen tension during oocyte/embryo manipulation was not under well control. For instance, oocyte retrieval, fertilization check and embryo grading were performed under atmospheric oxygen. It is difficult to predict how these factors negatively impact the IVF outcomes. In this project, the investigators hypothesize that lower oxygen tension during oocyte/embryo manipulation improves IVF outcomes.
Detailed Description
In the experimental group, oocyte pickup will be performed in a lower oxygen tension environment (5% oxygen, 89% nitrogen, 6% carbon dioxide); oocyte pickup will be performed in a special workstation with reduced oxygen tension environment while fertilization check and embryo grading will be performed in conventional and time lapse embryo culture system. The time lapse culture system can provide a constant lower oxygen tension culture environment to the embryos. In the control group, oocyte pickup, fertilization check and embryo grading will be performed in atmospheric oxygen environment. Under this arrangement, the difference between the 2 groups is the oxygen tension during oocyte/embryo manipulation. The investigators believe that a solid conclusion can be drawn about whether lower oxygen tension environment can benefit IVF outcomes.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Embryo Hypoxia

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
1160 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
20% O2
Arm Type
No Intervention
Arm Description
In the control group, oocyte pickup will be performed in atmospheric oxygen environment (20% oxygen, 89% nitrogen, 6% carbon dioxide).
Arm Title
5% O2
Arm Type
Experimental
Arm Description
In the experimental group, oocyte pickup will be performed in a low oxygen tension environment (5% oxygen, 89% nitrogen, 6% carbon dioxide). If time lapse embryo culture system is used, fertilization check and embryo grading will also be conducted under the low oxygen tension environment.
Intervention Type
Biological
Intervention Name(s)
5% O2
Intervention Description
5% oxygen will be used during oocyte retrieval, fertilization check and embryo grading
Primary Outcome Measure Information:
Title
live birth rate
Description
delivery of a live birth beyond 24 weeks of gestation
Time Frame
4 years
Secondary Outcome Measure Information:
Title
clinical pregnancy rate
Description
presence of at least one gestational sac on ultrasound of 6 weeks
Time Frame
3 years
Title
ongoing pregnancy rate
Description
presence of at least heart pulsation on ultrasound beyond 20 weeks
Time Frame
3 years
Title
fertilization rate
Description
No. of fertilized oocyte divided by No. of inseminated cumulus-oocyte complexes (COCs)
Time Frame
3 years
Title
cleavage rate
Description
No. of cleaved embryo divided by No. of fertilized oocyte
Time Frame
3 years

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: all the couples undergoing conventional IVF cycle in the reproductive medicine center of the University of Hong Kong-Shenzhen Hospital Exclusion Criteria: Intracytoplasmic sperm injection (ICSI) cycle Preimplantation genetic testing (PGT) cycle cycle with fertilization failure ≥3 cycle using sperm from percutaneous epididymal sperm aspiration (PESA)/testicular sperm extraction (TESE) or cryopreserved sperm cycle using cryopreserved oocyte cycle with no oocyte retrieved
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Qian Peng, PhD
Phone
8675586917836
Email
qianpeng_77@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shubiu Yeung, PhD
Organizational Affiliation
The University of Hong Kong-Shenzhen Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Reproductive medicine center
City
Shenzhen
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
QIAN PENG, PHD
Email
qianpeng_77@hotmail.com

12. IPD Sharing Statement

Citations:
PubMed Identifier
8107053
Citation
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.
Results Reference
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PubMed Identifier
18681997
Citation
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.
Results Reference
background
PubMed Identifier
18554591
Citation
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.
Results Reference
background

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Influence of Manipulation of Oocytes and Embryos in Low Oxygen Tension on Assisted Reproduction Technology Outcome

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