Optimizing the Temperature for Embryo Culture in In Vitro Fertilization

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Reproductive Medicine Associates of New Jersey
ClinicalTrials.gov Identifier:
NCT01506089
First received: January 3, 2012
Last updated: June 30, 2014
Last verified: June 2014
  Purpose

Many human and animal studies over the past 40 years have revealed that ovaries and Fallopian tubes have a lower temperature than core body temperature, especially around the time of ovulation and early embryo development. Whether average core body temperature, 37 degrees Celsius, is ideal temperature for culture has not been prospectively evaluated. The purpose of this study is to determine whether lowering the incubator temperature by 1 degree Celsius will result in meaningful improvements in embryo development and pregnancy rates.

Patients participating in this study will undergo routine in vitro fertilization (IVF) stimulation. Following egg retrieval, patients with at least 8 mature eggs will have those eggs divided randomly into two groups. Both groups will then under ICSI (intra-cytoplasmic sperm injection) to fertilize the eggs. The groups will randomly be assigned to control or study condition. The control condition group will be cultured at 37 degrees Celsius, the current standard of care. The study group will be cultured at 36 degrees Celsius. All other culture conditions will be kept identical and embryos will be assessed on day 3 and day 5 of development.

On day 5, all well-developed blastocysts will undergo biopsy for Comprehensive Chromosomal Screening (CCS), which will evaluate the chromosomal normalcy of the embryo . Patients will undergo transfer on the morning of day 6 and the highest quality, chromosomally normal embryo from each group (the 36 degree cultured embryos and the 37 degree cultured embryos) will be transferred. If only 1 embryo is available for transfer, the patient will have a single embryo transfer.

All embryos available for cryopreservation will undergo biopsy for CCS before being frozen. Some arrested embryos from each temperature group will also undergo genetic analysis to evaluate chromosomal normalcy or mosaicism.

The female patient will undergo a blood draw at 9 weeks gestation and buccal swabs will be obtained from the infant(s) after birth.


Condition Intervention
Infertility
Other: 36 degrees Celsius

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: Optimizing the Temperature for Embryo Culture in In Vitro Fertilization: A Randomized Controlled Trial

Resource links provided by NLM:


Further study details as provided by Reproductive Medicine Associates of New Jersey:

Primary Outcome Measures:
  • Useable Blastocyst Formation Rate [ Time Frame: approximately 1 week ] [ Designated as safety issue: No ]
    Proportion of mature eggs developing into expanded blastocysts (Gardner grade 3-6) of sufficient quality to transfer or cryopreserve will be documented for each group (36 degree and 37 degree group).


Secondary Outcome Measures:
  • Fertilization rate [ Time Frame: approximately 2 days ] [ Designated as safety issue: No ]
    The proportion of mature eggs that underwent ICSI and are normally fertlized (documented as forming 2 pro-nuclei (2PNs)) on the day after egg retrieval will be documented for each group (36 degree and 37 degree groups)

  • Cleavage Rate [ Time Frame: approximately 1 week ] [ Designated as safety issue: No ]
    Proportion of properly fertlized embryo (2PNs on day 1) that undergo further celluar division will be documented for each group (36 degree and 37 degree group).

  • Blastocyst Formation Rate [ Time Frame: approximately 1 week ] [ Designated as safety issue: No ]
    Proportion of mature oocytes that go on to develop into blastocysts in each group (36 degree group and 37 degree group) will be documented.

  • Implantation Rate [ Time Frame: approximately 2 weeks ] [ Designated as safety issue: No ]
    Proportion of transferred embryos resulting in a clinically documented pregnancy will be documented for each group (36 degree and 37 degree group).

  • Aneuploidy Rate [ Time Frame: approximately 1 month ] [ Designated as safety issue: No ]
    Rate of chromosomal abnormalities among the embryos in each group (36 degree and 37 degree groups) as determined by polymerase chain reaction (PCR) based comprehensive chromosome screening (CCS).

  • Mosaicism Rate [ Time Frame: approximately 1 month ] [ Designated as safety issue: No ]
    Proportion of embryos that arrest at the cleavage stage which show evidence of more than one chromosomal lineages (mosaicism) when analyzed my microarray documented in each group (36 degree and 37 degree group).


Estimated Enrollment: 100
Study Start Date: January 2012
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 36 degree group
36 degrees Celsius for the incubators is the experimental condition in this study.
Other: 36 degrees Celsius
Embryos in this group will be cultured in incubators set to 36 degrees Celsius.
Other Name: IVF, PGD, embryos, culture, CCS, infertility
No Intervention: 37 degree group
37 degrees Celsius is the standard incubator temperature for the culture of embryos.

  Eligibility

Ages Eligible for Study:   18 Years to 41 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • No more than 1 prior failed cycle at RMA NJ facility; up to 2 prior failed cycles at another facility pending investigator review
  • Female partner between 18 and 41 at onset of IVF cycle
  • Normal day 3 FSH (< or = 12) in RMA NJ laboratory
  • Basal antral follicle count of at least 10
  • Male partner with greater than 100,000 total motile spermatozoa per ejaculate (donor sperm is ok)
  • BMI < or = 32 kg/m2

Exclusion Criteria:

  • Diagnosis of chronic anovulation (cycles occuring typically less often than every 90 days)
  • Use of testicular aspiration or biopsy procedures to obtain sperm
  • Unevaluated ovarian mass or diagnosis of surgically-confirmed stage IV endometriosis
  • Presence of hydrosalpinges that communicate with the uterine cavity
  • History of endometrial insufficiency
  • Any contraindication to undergoing IVF or gonadotropin stimulation
  • Prior poor fertilization rate- less than 50% of mature eggs
  • Prior poor blastulation rate- less than 10% of 2PNs (day 1 embryos)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01506089

Locations
United States, New Jersey
Reproductive Medicine Associates of New Jersey
Morristown, New Jersey, United States, 07960
United States, Pennsylvania
Reproductive Medicine Associates of Pennsylvannia
Allentown, Pennsylvania, United States, 18104
Sponsors and Collaborators
Reproductive Medicine Associates of New Jersey
Investigators
Principal Investigator: Richard T Scott, MD Reproductive Medicine Associates of New Jersey
  More Information

Additional Information:
No publications provided

Responsible Party: Reproductive Medicine Associates of New Jersey
ClinicalTrials.gov Identifier: NCT01506089     History of Changes
Other Study ID Numbers: RMA-2011-02
Study First Received: January 3, 2012
Last Updated: June 30, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Reproductive Medicine Associates of New Jersey:
IVF
infertility
PGD
embryo
temperature
incubator
CCS
culture
incubator-36 degrees Celsius
incubator-37 degrees Celsius

Additional relevant MeSH terms:
Infertility
Genital Diseases, Male
Genital Diseases, Female

ClinicalTrials.gov processed this record on July 22, 2014