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

Santos‐Ribeiro 2020.

Study characteristics
Methods Single‐centre RCT
Conducted: in Belgium 
Enrolment: May 2014‐2017
Power calculation: stated
Randomisation: performed using a computer‐generated randomisation list (SPSS Version 20VR, IBM Corporation, New York, USA). Each entry of
the list was sealed in a sequentially numbered opaque envelope and allocated in that order to women. Participating physicians did not have access to the randomisation list.
Timing of randomisation: prior to oocyte retrieval
Nature of intervention: vitrification 
Follow‐up: 24 months after randomisation 
Participants 212 women (106 freeze‐all, 106 control)
Inclusion criteria: women with an excessive response to ovarian stimulation (≥ 18 follicles measuring ≥ 11 mm on the day of the GnRH triggering), GnRH antagonist suppression, age between 18‐40 years, first/second ART cycle in the centre, planned placement of 1 or 2 blastocysts. 
Interventions Intervention: all viable embryos were vitrified, preferably at blastocyst stage (Day 5 or 6), according to the threshold of good‐quality embryos available on day 3. After thaw, 1 or 2 frozen embryo(s) were transferred, scheduled according to the developmental stage of the embryo.
Control: fresh transfer of day 3 or 5 of development with preference to the latter whenever at least 4 good‐quality embryos were available on day 3.
In women who were assigned to the fresh embryo group, luteal‐phase support was started immediately after oocyte retrieval and was continued until the day of serum hCG testing. On day 2 or 3 of the embryo culture, up to 2 embryos were selected and transferred.
In women who were assigned to the FET group, all the embryos were vitrified. 2 good‐quality embryos were vitrified on day 2 or day 3, and the other embryos could be vitrified at the cleavage or blastocyst stage. At the second spontaneous menstrual cycle after oocyte retrieval, natural ovulation was monitored by means of ultrasonography. Luteal‐phase support was started from the day of ovulation. Up to two day 2 or day 3 frozen embryos were thawed and transferred 2 or 3 days, after ovulation. If the natural ovulation cycle was cancelled owing to anovulation or poor endometrial development, an artificial cycle was used for endometrial preparation in the next menstrual cycle.
Outcomes
  • Clinical pregnancy at 7 weeks of gestational age; defined as the visualisation of ≥ 1 gestational sacs (including an ectopic pregnancy) during transvaginal ultrasound

  • hCG‐positive (assessed in the serum 12–14 days after ET)

  • LBR (after 24 weeks)

  • Incidence of moderate to severe OHSS

  • Biochemical pregnancy 

  • Clinical miscarriage

  • Ectopic pregnancy

Notes Funding: this research received no specific grant from any funding agency in the public, commercial or not‐for‐profit sectors.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk By means of a computer‐generated randomisation list (SPSS Version 20VR, IBM Corporation, New York, USA)
Allocation concealment (selection bias) Low risk Each entry of the list was sealed in a sequentially numbered opaque envelope and allocated in that order to women. Participating physicians did not have access to the randomisation list.
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 Low risk Data were analysed for all randomised women according to ITT. 
Selective reporting (reporting bias) Low risk All registered outcomes reported.
Study was registered in a prospective trials register with the trial number: NCT02148393.
Other bias Low risk The study appears to be free of other sources of bias.