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. 2021 Feb 4;2021(2):CD011184. doi: 10.1002/14651858.CD011184.pub3

Shapiro 2011a.

Study characteristics
Methods Single‐centre RCT
Conducted: USA
Enrolment: October 2007‐October 2010
Power calculation: stated. However, study was prematurely terminated after interim analysis
Randomisation: performed by random drawing among identical, opaque, unmarked sealed envelopes
Timing of randomisation: after oocyte retrieval
Nature of intervention: slow freezing
Follow‐up: clinical pregnancy after first ET
Participants 137 women (70 freeze‐all, 67 fresh transfer)
Inclusion criteria:
  • Women must be undergoing her first IVF cycle

  • Cycle day 3 FSH < 10 IU/L

  • 8‐15 antral follicles observed on baseline ultrasound scan


Exclusion criteria: genetic testing of embryos was excluded.
Interventions Intervention: 2pn oocytes were frozen, and entire cohorts of frozen 2pn oocytes were thawed and subsequently cultured to the blastocyst stage. The morphologically best 1 or 2 blastocysts were transferred on the first day on which at least 1 good expanded blastocyst appeared. Supernumerary expanded blastocysts of high quality were cryopreserved.
Control: fresh blastocysts transfer
Outcomes
  • Pregnancy: serum hCG levels within 10 days after blastocyst transfer

  • Clinical pregnancy: fetal heart motion at 7 weeks' gestation

  • Ongoing pregnancy: fetal heart motion at 10 weeks' gestation

  • Implantation rate: proportion of transferred blastocysts that resulted in fetal heart motion (monozygotic twins with fetal heart motion counted as single implantations)

  • Early pregnancy losses: pregnancies that did not become ongoing pregnancies

Notes Funding: research grant from the Investigator‐Initatiated trial research grant from Ferring Pharmaceuticals, Parsippany, NJ. Medications for this study were also provided by Ferring Pharmaceuticals.
Time period was obtained from trials register
Additional information was obtained from study authors by email.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk Random sequence generation was not reported.
Allocation concealment (selection bias) Low risk Drawing randomly among identical, opaque, unmarked, sealed envelopes.
Blinding of participants and personnel (performance bias)
All outcomes Low risk Blinding of doctors and participants was not possible due to the nature of the intervention.
Blinding of outcome assessment (detection bias)
All outcomes Low risk Outcome assessor blinding was not reported, however primary outcome is not likely to be influenced by lack of blinding.
Incomplete outcome data (attrition bias)
All outcomes Unclear risk Data were not reported for all women randomised, but per transfer. Dropouts and loss to follow‐up were not accounted for in the analysis. No ITT analysis was performed. Sufficient data available for analysis per woman in meta‐analysis. Ongoing pregnancy was determined at 10 weeks' gestation instead of 12 weeks' gestation.
Selective reporting (reporting bias) Low risk All registered outcomes reported
Study was registered in a prospective trials register with the trial number: NCT00963625.
Other bias Unclear risk Study was pre‐terminated after interim analysis. Interim analysis was preplanned, but calculated per transfer (unit of analysis error) with a P value of 0.03, overestimating possible effects.
(Cumulative) data per subsequent menstrual or cryo‐transfer cycle not reported (relevant for time‐to‐pregnancy comparison and the related comparison of results after first transfer in FET group vs results after first 2 transfers in fresh group).