Live Births With Low Oxygen Blastocyst Culture
Condition: Infertility; Pregnancy Rate, Live Birth; In Vitro Fertilization
MeSH terms: Infertility
Study type: Interventional

Summary: 
      The potentially damaging effect of free O2 radicals to cultured embryos may be reduced by
      adding scavengers to the culture media or by reducing the incubator O2 levels. However,
      lowering the O2 in the culture environment can be expensive, troublesome and may not be
      justifiable. The objective of this study is to evaluate the effect of lowered incubator O2
      tension on live birth rates in a predominately day-5 embryo transfer program. The hypothesis
      of this study is that a lowered (more physiological)oxygen concentration in embryo culture
      incubators will increase live birth rates for in vitro fertilization patients. 230
      first-cycle women undergoing routine IVF or ICSI with ejaculated sperm will be randomized in
      a prospective clinical trial and stratified for patient age and physician. Embryos of
      patients will be randomly assigned for culture in either a 21% O2 (atmospheric) or 5% O2
      (reduced) environment. Clinical endpoints monitored will be rates of implantation, clinical
      pregnancy, live birth and blastocyst cryopreservation.
    

Detailed description: 
      Purpose: The purpose of this study is to determine if a more physiological oxygen
      concentration (5%) will improve clinical outcomes when compared with the industry standard of
      21%.

      Background: For embryos to grow in the incubator, atmospheric gas concentrations should be as
      close to possible to those seen in the oviduct or uterus. Currently, atmospheric
      (non-physiological, 21%) oxygen concentrations are used in the incubators to culture the
      embryos of infertility patients of the Presbyterian ARTS laboratories. Literature suggest
      that culturing animal embryos in a reduced oxygen environment will significantly improve
      embryo quality and clinical outcomes. Both 5% and atmospheric oxygen concentrations are
      routinely used for embryo culture in the human IVF laboratories, however, very few commercial
      human IVF facilities invest in oxygen control as it is more expensive to maintain and labor
      intensive to implement. The goal is to use lower oxygen concentrations in the future if
      clinical improvement justifies the expense and increased labor associated with low oxygen
      culture.

      Project Summary: Study design: The study will be conducted in a prospective, randomized way.
      Two treatment groups are considered: 1) existing atmospheric oxygen concentration in embryo
      incubators 2) lower 5% oxygen concentration in embryo culture incubators. To allow for the
      well-documented decline in pregnancy rates with increased age, patients will be stratified
      within 4 age groups and 3 physicians within each treatment. The age groups are: donor eggs;
      <35 years; 35 to 37 years; and 38 to 40 years as determined on the day of egg retrieval.

      Endpoints Measured: The endpoints measured will be embryo cryopreservation-biochemical
      pregnancy-, clinical pregnancy-, ongoing pregnancy-, live birth- and embryo implantation
      rates.

      Number of Patients in the Study: To detect a difference of 10% in pregnancy rates, 150
      patients should be included in each treatment group. With the current patient volume, it
      should take less than one year to complete the study. Differences in implantation rates may
      be detected earlier (more embryos transferred than patients enrolled). Should significance
      differences in pregnancy rates become evident before the full number of patients is enrolled,
      the study may be terminated.

      Study Location: The study will be conducted at the ARTS facility of Presbyterian Hospital of
      Plano.

      Criteria for Inclusion of Subjects: All patients undergoing a first IVF cycle or any donor
      oocyte cycle is eligible to participate in this laboratory comparison. The eggs may be
      fertilized with conventional IVF methodology or by using intracytoplasmic sperm injection
      (ICSI). When performing ICSI, ejaculated sperm must be used. Patients using their own eggs
      must be 40 years of age or younger on the day of egg retrieval. The Presbyterian Hospital
      ARTS Program performed ~900 egg retrievals in 2000. Of these, ~500 would have met the
      inclusion criteria of this study.

      Criteria for Exclusion of Subjects: To reduce the tremendous patient variability seen in the
      infertile patient population, only first cycle patients 40 years of age or younger on the day
      of egg retrieval should participate.

      Sources of Research Material: Patients will be enrolled in this study from the regular
      patient pool presented to the Presbyterian ARTS Program for treatment of infertility. Data
      will not be collected specifically for research purposes. Data to be used are collected on
      all ARTS patients, regardless of participation in the study.

      Recruitment of Subjects: Subjects for this study will be recruited from the regular patient
      pool presented to the ARTS Program for the treatment of infertility. Patients that will meet
      the inclusion criteria of this study can be identified prospectively. Information about the
      study will be included in the routine, biweekly, group laboratory and nursing orientation
      sessions.

      Potential Risks: Patients consenting to the comparison will allow their embryos to be
      cultured in either the standard atmospheric oxygen concentration or in a reduced, more
      physiological oxygen concentration. Atmospheric (21%) oxygen concentrations is the current
      standard in this program. Both methods are considered industry standard. To our best
      knowledge and as reported in animal literature, low oxygen culture should do better rather
      than worse under the conditions proposed for this study. No other culture conditions or
      culture media compositions/ingredients that will be applied during this comparison is
      experimental. However, when atmospheric oxygen concentrations and lowered (5%) oxygen
      concentrations are compared in a controlled, randomized way as suggested in this comparison,
      the ARTS Program can not guarantee that the pregnancy outcome will be equivalent for both
      treatment groups. Therefore, by being randomized, a patient may be included in a group with a
      lower success rate.

      Special Precautions: If it should become clear early in the study that either one of the
      treatments are superior to the other, the study will be discontinued and the best conditions
      implemented for future patients.
    

Intervention name(s): Embryo incubator oxygen concentration
Intervention type(s): Other
Intervention description(s): Two concentrations of oxygen are currently used to culture the embryos of infertile patients in commercial human IVF programs - 21% and 5%.
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: in vitro fertilization; oxygen concentration; blastocyst; live birth; embryo