ACTRN12616000643471.

Study name	Comparison of the probability of live birth after elective freezing of all embryos versus standard fresh embryo transfer in patients undergoing in‐vitro fertilisation (IVF)
Methods	RCT Target enrolment: 400
Participants	Women aged 18‐39 with indication for COS and IVF or ICSI with autologous gametes Key inclusion criteria: Age: 18‐39 years BMI: 18‐32 kg/m2 Presence of both ovaries Normal menstruating cycles: 21‐35 days Cycle where prevention of premature LH rise is achieved using a GnRH antagonist 8‐19 follicles ≥ 10 mm in mean diameter on the day of triggering Key exclusion criteria: Endometriosis stage > II Indication for PGD/PGS History of OHSS Previous participation in the RCT > 3 previous unsuccessful stimulated cycles History of hypothalamic dysfunction or history of inadequate pituitary response to GnRH agonist triggering
Interventions	Interventional freeze‐all group Triggering of final oocyte maturation will be performed in the freeze‐all arm with a bolus subcutaneous injection of 2 mg of leuprolide acetate when at least 3 follicles ≥ 17mm in mean diameter are present at ultrasound. Oocyte retrieval will be performed at 34‐36 h after leuprolide administration. Embryos will be cultured for 5 days using the standard protocol of each clinic. All day‐5 embryos of top and good quality (at least at early blastocyst stage and of ICM/trophectoderm: AA, AB, BA, BB) will be cryopreserved using the method of vitrification. Delayed embryos will be allowed to be vitrified on day 6 as long as they fulfil the quality criteria (at least at early blastocyst stage and of ICM/trophectoderm: AA, AB, BA, BB). Based on the pre‐vitrification morphological quality, the best blastocyst will be thawed for the next ET. If the blastocyst does not survive, the next best blastocyst (based again on the pre‐vitrification morphological criteria) will be thawed. The maximum period of embryo cryopreservation is theoretically indefinite, however it rarely exceeds 5 years. For the primary outcome of this study, the embryo cryopreservation period is estimated between 20 days‐3 months. Hence, thawing and ET is expected to occur within this timeframe. Fresh transfer group Triggering of final oocyte maturation will be performed in the fresh transfer arm with a bolus subcutaneous injection of 250 mcg of r‐hCG when at least three follicles of equal to or greater than 17mm in mean diameter are present at ultrasound. Oocyte retrieval will be performed at 34‐36h after r‐hCG administration. Embryos will be cultured for 5 days using the standard protocol of each clinic. On day 5 of embryo culture the developmental stage and quality of the blastocysts will be recorded including ICM and trophectoderm grading. The morphologically best day‐5 embryo (according to the judgement of the embryologist) will be transferred. All remaining day‐5 embryos of top and good quality (at least at early blastocyst stage and of ICM/trophectoderm: AA, AB, BA, BB) will be cryopreserved using the method of vitrification. Delayed embryos will be allowed to be vitrified on day 6 as long as they fulfil the quality criteria (at least at early blastocyst stage and of ICM/trophectoderm: AA, AB, BA, BB).
Outcomes	Live birth after the transfer of the first embryo: delivery of a live baby after the 20th week of gestation Ongoing pregnancy diagnosed by ultrasonography as presence of fetal heart activity at 10‐12 weeks of gestation Clinical pregnancy diagnosed by ultrasound as presence of fetal heart activity at 6‐8 weeks of gestation First trimester miscarriage, defined as a biochemical pregnancy (assessed by serum hCG) at 11‐16 days after ET but no fetal heart activity at 10‐12 weeks of gestation as assessed by ultrasonography Occurrence of severe OHSS Preterm labour (defined as delivery < 37 weeks of gestation) Mode of delivery (normal vaginal delivery, assisted vaginal delivery, caesarean section) Neonatal birth weight Stillbirth Neonatal mortality Death within the first 28 days of life Intrauterine growth restriction Hypertensive disorders of pregnancy (including gestational hypertension, pre‐eclampsia, eclampsia) Gestational diabetes mellitus
Starting date	May 2016
Contact information	Christos Venetis: c.venetis@unsw.edu.au
Notes	www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12616000643471