title: A pilot double-blind randomised placebo-controlled dose-response trial assessing the effects of melatonin on infertility treatment (MIART): study protocol.
abstract: BACKGROUND
  High levels of oxidative stress can have considerable impact on the outcomes of in vitro fertilisation (IVF). Recent studies have reported that melatonin, a neurohormone secreted from the pineal gland in response to darkness, has significant antioxidative capabilities which may protect against the oxidative stress of infertility treatment on gametes and embryos. Early studies of oral melatonin (3-4 mg/day) in IVF have suggested favourable outcomes. However, most trials were poorly designed and none have addressed the optimum dose of melatonin. We present a proposal for a pilot double-blind randomised placebo-controlled dose-response trial aimed to determine whether oral melatonin supplementation during ovarian stimulation can improve the outcomes of assisted reproductive technology.
  
  
  METHODS
  We will recruit 160 infertile women into one of four groups: placebo (n=40); melatonin 2 mg twice per day (n=40); melatonin 4 mg twice per day (n=40) and melatonin 8 mg twice per day (n=40). The primary outcome will be clinical pregnancy rate. Secondary clinical outcomes include oocyte number/quality, embryo number/quality and fertilisation rate. We will also measure serum melatonin and the oxidative stress marker, 8-hydroxy-2'-deoxyguanosine at baseline and after treatment and levels of these in follicular fluid at egg pick-up. We will investigate follicular blood flow with Doppler ultrasound, patient sleepiness scores and pregnancy complications, comparing outcomes between groups. This protocol has been designed in accordance with the SPIRIT 2013 Guidelines.
  
  
  BACKGROUND
  Ethical approval has been obtained from Monash Health HREC (Ref: 13402B), Monash University HREC (Ref: CF14/523-2014000181) and Monash Surgical Private Hospital HREC (Ref: 14107). Data analysis, interpretation and conclusions will be presented at national and international conferences and published in peer-reviewed journals.
  
  
  BACKGROUND
  ACTRN12613001317785.
authors.affiliation: MIMR-PHI Institute of Medical Research, Clayton, Victoria, Australia Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia Department of Obstetrics and Gynaecology, Level 5 Monash Medical Centre, Clayton, Victoria, Australia.
authors.forename: Shavi
authors.initials: S
authors.lastname: Fernando
authors.affiliation: Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia Monash IVF, Clayton, Victoria, Australia.
authors.forename: Tiki
authors.initials: T
authors.lastname: Osianlis
authors.affiliation: Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia Department of Obstetrics and Gynaecology, Level 5 Monash Medical Centre, Clayton, Victoria, Australia.
authors.forename: Beverley
authors.initials: B
authors.lastname: Vollenhoven
authors.affiliation: MIMR-PHI Institute of Medical Research, Clayton, Victoria, Australia Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia Department of Obstetrics and Gynaecology, Level 5 Monash Medical Centre, Clayton, Victoria, Australia.
authors.forename: Euan
authors.initials: E
authors.lastname: Wallace
authors.affiliation: MIMR-PHI Institute of Medical Research, Clayton, Victoria, Australia Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia Monash IVF, Clayton, Victoria, Australia.
authors.forename: Luk
authors.initials: L
authors.lastname: Rombauts
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D005306:Fertilization / Q000187:drug effects; D006801:Humans; D007247:Infertility, Female / Q000188:drug therapy* / Q000628:therapy; D008550:Melatonin / Q000494:pharmacology / Q000627:therapeutic use*; D009865:Oocytes; D010062:Ovulation Induction / Q000379:methods*; D018384:Oxidative Stress / Q000187:drug effects*; D010865:Pilot Projects; D011247:Pregnancy; D018873:Pregnancy Rate; D012107:Research Design
chemical_list: D000975:Antioxidants; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D008550:Melatonin