NCT03349905.

Study name	Deferred versus fresh embryo transfers (DEFETOSE)
Methods	RCT Estimated enrolment: 2294
Participants	Women aged 18‐40 Inclusion criteria: Women eligible for ovarian stimulation and ART treatment, including ICSI Absence of anatomical abnormalities of the reproductive tract that would interfere with implantation or pregnancy Absence of any medical condition in which pregnancy is contraindicated Motile, ejaculatory sperm must be available (donated and/or cryopreserved sperm is allowed) ICSI will be allowed during this trial BMI 18‐35 kg/m2, inclusive Able to understand the study Affiliation with a social security scheme Dated and signed inform consent Exclusion criteria: Altered ovarian reserve (day 3: FSH > 12 UI/L; AMH < 1.0 ng/mL; AFC < 8) History or presence of tumours of the hypothalamus or pituitary gland Presence of non isolated uni‐ or bilateral hydrosalpinx Abnormal gynaecological bleeding of undetermined origin Contraindication to being pregnant and/or carrying a pregnancy to term Known infection with HIV, active HBV or HCV in the female or male partner History or presence of ovarian, uterine or mammary cancer Known allergy or hypersensitivity to human gonadotropin preparations or to compounds that are structurally similar to any of the other medications administered during the trial Substance abuse that would interfere with trial conduct, as determined by the investigator Use of testicular or epididymal sperm Pregnant patient, nursing patient Participation in another ART clinical trial within the past 30 days Women who have risk to develop severe OHSS during COS defined as ≥ 18 follicles measuring 10‐14 mm on the day of triggering Women with < 3 follicles ≥ 15 mm on the triggering day or the day before the triggering Women with premature progesterone elevation during COS ( ≥ 1.5 ng/mL) Women with uterine polyps diagnosed during COS Participation with another interventional study involving human participants
Interventions	Fresh transfer Antagonist stimulation protocol Ovarian triggering using a single injection of r‐hCG (Ovitrelle®; Serono, France) All of their embryos kept in prolonged culture A fresh single ET at blastocyst stage (on day 5 or 6 according to blastocyst stage) Supernumerary blastocysts cryopreserved Deferred‐frozen ET Antagonist stimulation protocol Ovarian triggering using a single injection of 0.2 mg of GnRH agonist triptorelin (Decapeptyl® Ipsen France) All of their embryos cryopreserved at the blastocyst stage after prolonged embryo culture A frozen‐thawed single ET at blastocyst stage, is planned 4‐5 weeks after cryopreservation
Outcomes	LBRs: cut‐off of 35 weeks postmenstrual age is to ensure the health and well‐being of the newborn babies Miscarriage: intrauterine clinical pregnancy that occurs before 20 completed weeks postmenstrual age (18 weeks post fertilisation) Clinical pregnancy: defined as a pregnancy diagnosed by ultrasonographic visualisation of ≥ 1 gestational sacs or definitive clinical signs of pregnancy. It includes ectopic pregnancy Preterm birth: defined as a live birth or stillbirth that takes place after at least 20 but before 37 completed weeks of postmenstrual age Preterm rupture of membranes Pre‐eclampsia Placenta praevia LBRs in endometriosis‐related infertility Number of oocytes retrieved Number of MII oocytes Number of embryos Number of blastocysts Number of transferred blastocysts The cancellation rate The rate of started pregnancy The rate of pregnancy confirmed by the echography (cardiac activity) Started pregnancy defined by a rate of hCG > 100 Rate of multiple pregnancy Implantation rate: defined as the number of gestational sacs seen via transvaginal ultrasonography 4‐5 weeks after ET, per number of embryos transferred Cryopreservation thaw rate: defined as percentage of vitrified blastocysts that survive warming The incremental cost effectiveness ratio using LBR as the effectiveness endpoint, after 35 weeks
Starting date	September 2018
Contact information	Pietro SANTULLI, MD, PhD: pietro.santulli@aphp.fr Christelle AUGER: christelle.auger@aphp.fr
Notes	https://clinicaltrials.gov/ct2/show/NCT03349905

AFC: antral follicle count; AMH: anti‐Müllerian hormone; ART: assisted reproductive technology; BMI: body mass index; COS: controlled ovarian stimulation; ET: embryo transfer; FET: frozen embryo transfer; FSH: follicle‐stimulating hormone; GnRH: gonadotropin‐releasing hormone; HBV: hepatitis B virus; hCG: human chorionic gonadotropin; HCV: hepatitis C virus; ICM: inner cell mass; ICSI: intracytoplasmic sperm injection; HSG: hysterosalpingogram; IVF: in vitro fertilisation; LH: luteinising hormone; OHSS: ovarian hyperstimulation syndrome; PCOS: polycystic ovary syndrome; PGD: pre‐implantation genetic diagnosis; PGS: pre‐implantation genetic screening; PRL: prolactin; r‐hCG: recombinant human chorionic gonadotropin; RCT: randomised controlled trial; SHBG: sex hormone‐binding globulin; TSH: thyroid‐stimulating hormone