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. 2019 Sep 17;2019(9):CD012192. doi: 10.1002/14651858.CD012192.pub2

Hong 2014.

Methods Study design: randomised controlled trial
Study grouping: parallel group
Participants Baseline Characteristics
36.0°C
  • Number of oocytes: 399


37.0°C (control group)
  • Number of oocytes: 406


Total number of participants: 70 couples. 18 patients had fewer than eight mature oocytes isolated at the time of retrieval and were not eligible to participate. 52 infertile couples with a female partner less than 42 years old with eight or more mature oocytes retrieved. No further characteristics found on the 52 infertile couples. A total of 805 mature oocytes were cultured, 399 at 36 degrees and 306 at 37 degrees.
Inclusion criteria
Inclusion criteria reflected the paired design of the study.
  • Age ≤ 42 years old at the time of the patient's IVF cycle

  • No more than one prior failed fresh IVF cycle

  • Patient < 35 years old who was deemed not to be ideal elective single embryo transfer candidate by their treating physician due to history of a prior failed IVF cycle

  • A minimum of eight oocytes with nuclear maturity (MII) at the time of oocyte denudation


Exclusion criteria
  • Severe male factor infertility requiring surgical sperm extraction

  • Chronic anovulation

  • BMI > 32 kg/m2

  • Abnormal uterine cavity

  • A prior history of poor fertilisation (< 50% of MII oocytes fertilising normally)

  • A prior history of poor blastulation (< 10% of zygotes blastulating)


"Infertile couples attempting conception through IVF at Reproductive Medicine Associates of New Jersey (RMANJ) from February 2012 to December 2012 were evaluated by physicians and the clinical research team to determine their eligibility to participate in the study. Participants were observed until delivery."
 
 "Patients were sought who would likely produce sufficient oocytes to have several mature oocytes in each of the study groups so that each patient might effectively serve as her own control. The paired nature of the experimental design ultimately provided quality between two groups of oocytes from a single patient in a single cycle as they experienced identical endocrine milieus during follicular stimulation. Each patient's cohort of mature oocytes was split into two dishes of equivalent number and morphology (based on the embryologist's subjective assessment of cytoplasmic granularity, polar body morphology, and appearance of the zona pellucida)."
Pretreatment:
Note that there were no restrictions on stimulation protocols.
Interventions Intervention characteristics
36.0°C
37.0°C (control group)
Outcomes Primary outcome
  • Proportion of zygotes with two pronuclei (2PN) that developed into expanded blastocysts suitable for either embryo transfer or cryopreservation


Secondary outcome
  • Rates of 2PN formation per MII oocyte

  • Number of cells in the cleavage‐stage embryo on day 3

  • Proportion of aneuploid embryos from each group per 2PN zygote

  • Sustained implantation rate (number of live births at ≥ 24 weeks gestation per embryo transferred)

Notes They reported no information about funding or competing interests. We requested further information about study design; this was provided by the authors.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Quote: "The authors used a random number function to generate a simple 1:1 randomisation to determine which of the dishes was assigned to the study group, undergoing culture at 36 C. The other dish was cultured at 37 C."
Allocation concealment (selection bias) Low risk Quote: "Allocation concealment was achieved using sequentially numbered, opaque, sealed envelopes."
Blinding of participants and personnel (performance bias) 
 All outcomes High risk Quote: "The embryologist performing grading and selecting embryos for transfer was not blinded to the temperature of culture." "The patients and physicians were aware of the plan for two embryo transfer of one from each group." Information provided by the 1st author on 13/03/2016
Blinding of outcome assessment (detection bias) 
 All outcomes Low risk Judgement comment: sustained implantation rate is an objective outcome.
Incomplete outcome data (attrition bias) 
 All outcomes Low risk Quote: "Seventy couples volunteered and were considered for participation in the study. Of these, 18 patients had fewer than eight mature oocytes isolated at the time of retrieval and were not eligible to participate. The remaining 52 patients were enrolled. No patients were lost to follow‐up observation. All delivery outcomes were available."
Quote: "An intent‐to‐treat analysis was performed to account for all patients, including those who did not undergo transfer."
Judgement comment: although no numbers of participants reported in method section, they explained loss to follow‐up and did intention‐to‐treat. Therefore low risk. Clarification of data provided from the first author on 13 March 2016
Selective reporting (reporting bias) High risk Judgement comment: Clinicaltrials NCT01506089; provided mosaicism rate as outcome data, not reported in this article. Quote: "rates of mosaicism cannot be directly determined."
Other bias Unclear risk Judgement comment: there is insufficient information to assess whether an important risk of bias exists

BMI ‐ body mass index
 HCG ‐ human chorionic gonadotropin
 ICSI ‐ intracytoplasmic sperm injection
 IVF – in vitro fertilisation