The Effects of Physiologic Oxygen Tension on Clinical In Vitro Fertilization Outcomes (PhOx)

A Prospective, Randomized, Double-Blind, Controlled Clinical Trial of the Effects of Oxygen Tension on Clinical In Vitro Fertilization Outcomes

Primary Aim

• Evaluate whether human embryo exposure to physiologic levels of oxygen during culture improves the percentage of women who deliver a baby following in vitro fertilization and embryo transfer.

Hypothesis to be tested: Physiologic oxygen tension during embryo culture, which approximates the oxygen tension in the fallopian tube and uterus, improves live birth rate in clinical In Vitro Fertilization Embryo Transfer (IVF-ET).

Secondary Aims

Evaluate whether human embryo exposure to physiologic levels of oxygen during culture during in vitro fertilization and embryo transfer

• improves embryo cleavage
• improves clinical pregnancy rate
• reduces multiple pregnancy rate
• reduces miscarriage rate

Hypothesis to be tested: Physiologic oxygen tension during embryo culture, which approximates the oxygen tension in the fallopian tube and uterus, improves embryo cleavage and clinical pregnancy rates and reduces miscarriage rates in clinical IVF-ET.

Study Overview

• Status: Completed
• Conditions: Infertility; Pregnancy
• Intervention / Treatment: Procedure: Atmospheric oxygen tension; Procedure: Physiologic oxygen tension

Detailed Description

Study Design

This will be a multi-center, prospective, double-blind clinical trial of physiologic (5%) oxygen tension in culture media vs. standard of care, atmospheric (SOC, 20%) oxygen tension with 840 eligible couples recruited to participate. The randomization scheme will be coordinated through the central data coordinating center (DCC-Yale) and the randomization will be stratified by age group of the woman (18-34, 35-37, 38-40 and 40-42) and each participating site.

Treatment

Couples will be randomized to either have their gametes and embryos placed in a physiologic (5%) oxygen atmosphere or in the currently widely used atmospheric (20%) oxygen atmosphere.

• Study Type: Interventional
• Enrollment (Actual): 851
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94115
      • University of California, San Francisco
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale University
    • Storrs, Connecticut, United States, 06269
      • University of Connecticut
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 42 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

The critical inclusion criteria will be the diagnosis of infertility and the need for in vitro fertilization as determined by the treating clinician. (We do not plan to alter the standard of care for the indication for IVF at any of the sites.)

• Couple's age must be between 18 and 42 years old
• Patient and partner are scheduled to undergo in vitro fertilization for treatment of infertility
• Couple able to participate in a research project and A) Able to understand study requirements B) Willing to sign informed consent C) Able to return for required follow-up D) Have access to telephone

Exclusion Criteria:

Critical exclusion criteria for this trial will be medical conditions which may complicate treatment or no plans to undergo embryo transfer, as in patients banking embryos prior to cancer therapy. In addition, donor egg and frozen embryo transfer cycles will be excluded.

• Medical contraindication to egg retrieval or pregnancy
• Inability to participate in a research project (Non-English speaking or unable to read or write and/or concurrent participation in any other interventional trial)
• Couple with more than three previous failed IVF cycles
• Donor egg and frozen embryo transfer cycles

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: atmospheric (20%) oxygen tension; Couples will have their gametes and embryos placed in the currently widely used atmospheric (20%) oxygen atmosphere	Procedure: Atmospheric oxygen tension; Couples will have their gametes and embryos placed in the currently widely used atmospheric (20%) oxygen atmosphere
Active Comparator: physiologic (5%) oxygen tension; Couples will have their gametes and embryos placed in a physiologic (5%) oxygen atmosphere	Procedure: Physiologic oxygen tension; Couples will have their gametes and embryos placed in a physiologic (5%) oxygen atmosphere

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary outcome is live birth rate.	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
The impact of treatment on embryo cleavage	2 years
The impact of treatment on clinical pregnancy	2 years
The impact of treatment on multiple pregnancy	2 years
The impact of treatment on miscarriage	2 years

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); University of Pennsylvania; University of California, San Francisco; University of Connecticut
• Investigators: Study Chair: Esther Eisenberg, MD, MPH, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Study Director: Marcelle Cedars, MD, University of California, San Francisco; Study Director: Nanette Santoro, MD, Albert Einstein College of Medicine; Principal Investigator: Christos Coutifaris, MD, PhD, University of Pennsylvania; Study Director: John Nulsen, MD, University of Connecticut

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: November 6, 2009
• First Submitted That Met QC Criteria: November 9, 2009
• First Posted (Estimate): November 10, 2009

Study Record Updates

• Last Update Posted (Actual): May 8, 2017
• Last Update Submitted That Met QC Criteria: May 5, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Infertility; Pregnancy; Physiologic Oxygen Tension; Atmospheric Oxygen Tension
• Additional Relevant MeSH Terms: Infertility
• Other Study ID Numbers: RMN-PhOx