Clinical trial NCT01506089: Optimizing the Temperature for Embryo Culture in In Vitro Fertilization
Official title: Optimizing the Temperature for Embryo Culture in In Vitro Fertilization: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Infertility
Keywords: IVF
infertility
PGD
embryo
temperature
incubator
CCS
culture
incubator-36 degrees Celsius
incubator-37 degrees Celsius
Lead sponsor: Reproductive Medicine Associates of New Jersey
Sponsor class: OTHER
First posted: 2012-01-09
Enrollment: 55
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 41
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief summary: 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.


Eligibility 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)

Primary outcomes:
measure: Useable Blastocyst Formation Rate
timeFrame: approximately 1 week
Secondary outcomes:
measure: Fertilization rate
timeFrame: approximately 2 days
measure: Cleavage Rate
timeFrame: approximately 1 week
measure: Blastocyst Formation Rate
timeFrame: approximately 1 week
measure: Implantation Rate
timeFrame: approximately 2 weeks
measure: Aneuploidy Rate
timeFrame: approximately 1 month
measure: Mosaicism Rate
timeFrame: approximately 1 month
Other outcomes:
Locations:
city: Morristown
country: United States
facility: Reproductive Medicine Associates of New Jersey
state: New Jersey
city: Allentown
country: United States
facility: Reproductive Medicine Associates of Pennsylvannia
state: Pennsylvania
Study officials:
affiliation: Reproductive Medicine Associates of New Jersey
name: Richard T Scott, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hong KH, Lee H, Forman EJ, Upham KM, Scott RT Jr. Examining the temperature of embryo culture in in vitro fertilization: a randomized controlled trial comparing traditional core temperature (37 degrees C) to a more physiologic, cooler temperature (36 degrees C). Fertil Steril. 2014 Sep;102(3):767-73. doi: 10.1016/j.fertnstert.2014.06.009. Epub 2014 Jul 17.