title: Cryo-thawed embryo transfer: natural versus artificial cycle. A non-inferiority trial. (ANTARCTICA trial).
abstract: BACKGROUND
  Frozen thawed embryo transfer (FET) is a cost-effective adjunct to IVF or IVF-ICSI treatment. In order to optimize treatment outcome, FET should be carried out during a period of optimal endometrial receptivity. To optimize implantation several methods for endometrium preparation have been proposed. In natural cycle FET (NC-FET), the endometrium develops under endogenous hormonal stimulation. The development of the dominant follicle and endometrium is monitored by ultrasound and FET is timed after triggering ovulation induction or determination of the spontaneous LH surge. In an artificial cycle FET (AC-FET) estrogens and progesterone are administered to prepare the endometrium for implantation. While the currently available data show no significant difference in pregnancy rates between these methods, well designed randomized controlled trials are lacking. Moreover there is little literature on difference in cancellation rates, cost-efficiency and adverse events.
  
  
  METHODS
  In this randomized, multi-centre, non-inferiority trial we aim to test the hypothesis that there is no significant difference in live birth rates between patients undergoing NC-FET versus AC-FET. The primary outcome will be live birth rate per embryo transfer procedure. Secondary outcomes will be ongoing and clinical pregnancy rate, cancellation rate, (serious) adverse events and cost-efficiency. Based on a live birth rate of 20% and a minimal clinical important difference of 7.5% (one-sided alpha 2.5%, beta 20%) a total of 1150 patients will be needed. Analyzes will be performed using both per protocol as well as intention to treat analyses.
  
  
  CONCLUSIONS
  This prospective, randomized, non-inferiority trial aims to address the hypothesis that there is no significant difference in live birth rates between patients undergoing NC-FET versus patients undergoing AC-FET. Moreover it addresses cost-efficiency as well as the perceived burden of both treatments.
  
  
  BACKGROUND
  Netherlands trial register (NTR): 1586.
authors.affiliation: UMCG, Groningen, The Netherlands. e.r.groenewoud@umcg.nl
authors.forename: Eva R
authors.initials: ER
authors.lastname: Groenewoud
authors.forename: Nick S
authors.initials: NS
authors.lastname: Macklon
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Cohlen
mesh_terms: D000293:Adolescent; D000328:Adult; D002985:Clinical Protocols; D003362:Cost-Benefit Analysis; D004334:Drug Administration Schedule; D004624:Embryo Transfer / Q000009:adverse effects / Q000191:economics / Q000379:methods*; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000191:economics; D004967:Estrogens / Q000008:administration & dosage / Q000191:economics; D005260:Female; D006801:Humans; D007247:Infertility, Female / Q000191:economics / Q000628:therapy*; D057194:Intention to Treat Analysis; D050498:Live Birth; D008597:Menstrual Cycle; D009426:Netherlands; D057240:Patient Preference; D011247:Pregnancy; D018873:Pregnancy Rate; D011374:Progesterone / Q000008:administration & dosage / Q000191:economics; D011372:Progestins / Q000008:administration & dosage / Q000191:economics; D016037:Single-Blind Method; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D004967:Estrogens; D011372:Progestins; D011374:Progesterone; D004958:Estradiol