{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T12:01:41Z","timestamp":1790942501883,"version":"4.1.0"},"reference-count":60,"publisher":"BMJ","issue":"8","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2014,8,11]]},"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      High levels of oxidative stress can have considerable impact on the outcomes of\n                      <jats:italic>in vitro<\/jats:italic>\n                      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\u20134\u2005mg\/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\u2013response trial aimed to determine whether oral melatonin supplementation during ovarian stimulation can improve the outcomes of assisted reproductive technology.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analyses<\/jats:title>\n                    <jats:p>We will recruit 160 infertile women into one of four groups: placebo (n=40); melatonin 2\u2005mg twice per day (n=40); melatonin 4\u2005mg twice per day (n=40) and melatonin 8\u2005mg 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\u2032-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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>ACTRN12613001317785.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2014-005986","type":"journal-article","created":{"date-parts":[[2014,9,1]],"date-time":"2014-09-01T21:06:49Z","timestamp":1409605609000},"page":"e005986","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":18,"title":["A pilot double-blind randomised placebo-controlled dose\u2013response trial assessing the effects of melatonin on infertility treatment (MIART): study protocol"],"prefix":"10.1136","volume":"4","author":[{"given":"Shavi","family":"Fernando","sequence":"first","affiliation":[{"name":"MIMR-PHI Institute of Medical Research, Clayton, Victoria, Australia"},{"name":"Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia"},{"name":"Department of Obstetrics and Gynaecology, Level 5 Monash Medical Centre, Clayton, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiki","family":"Osianlis","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia"},{"name":"Monash IVF, Clayton, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverley","family":"Vollenhoven","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia"},{"name":"Department of Obstetrics and Gynaecology, Level 5 Monash Medical Centre, Clayton, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Euan","family":"Wallace","sequence":"additional","affiliation":[{"name":"MIMR-PHI Institute of Medical Research, Clayton, Victoria, Australia"},{"name":"Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia"},{"name":"Department of Obstetrics and Gynaecology, Level 5 Monash Medical Centre, Clayton, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luk","family":"Rombauts","sequence":"additional","affiliation":[{"name":"MIMR-PHI Institute of Medical Research, Clayton, Victoria, Australia"},{"name":"Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia"},{"name":"Monash IVF, Clayton, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2014,9,1]]},"reference":[{"key":"2025121514001417000_4.8.e005986.1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867043455567"},{"key":"2025121514001417000_4.8.e005986.2","first-page":"219","article-title":"Studies on free radicals, antioxidants, and co-factors","volume":"2","author":"Rahman","year":"2007","journal-title":"Clin Interv Aging"},{"key":"2025121514001417000_4.8.e005986.3","doi-asserted-by":"publisher","DOI":"10.4161\/oxim.3.4.12858"},{"key":"2025121514001417000_4.8.e005986.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2006.07.001"},{"key":"2025121514001417000_4.8.e005986.5","doi-asserted-by":"crossref","unstructured":"Tamura H Takasaki A Taketani T . 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