Melatonin in Assisted Reproductive Technology: A Pilot Double-Blind Randomized Placebo-Controlled Clinical Trial
Purpose: To explore in a small pilot study whether oral melatonin, administered during ovarian stimulation increases clinical pregnancy rate (CPR) after IVF and what dose might be most effective.Methods: Pilot double-blind, dose-finding, placebo-controlled randomized clinical trial in private IVF cl...
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doaj-bbe77963513b4d3c8a9533fe491115132020-11-25T02:46:31ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922018-09-01910.3389/fendo.2018.00545395108Melatonin in Assisted Reproductive Technology: A Pilot Double-Blind Randomized Placebo-Controlled Clinical TrialShavi Fernando0Shavi Fernando1Euan Morrison Wallace2Euan Morrison Wallace3Beverley Vollenhoven4Beverley Vollenhoven5Nicholas Lolatgis6Nicole Hope7Melissa Wong8Mark Lawrence9Anthony Lawrence10Chris Russell11Kenneth Leong12Philip Thomas13Luk Rombauts14Luk Rombauts15Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC, AustraliaThe Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, AustraliaDepartment of Obstetrics and Gynaecology, Monash University, Clayton, VIC, AustraliaThe Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, AustraliaDepartment of Obstetrics and Gynaecology, Monash University, Clayton, VIC, AustraliaMonash IVF, Richmond, VIC, AustraliaMonash IVF, Richmond, VIC, AustraliaMonash IVF, Richmond, VIC, AustraliaMonash IVF, Richmond, VIC, AustraliaMonash IVF, Richmond, VIC, AustraliaMonash IVF, Richmond, VIC, AustraliaMonash IVF, Richmond, VIC, AustraliaMonash IVF, Richmond, VIC, AustraliaMonash IVF, Richmond, VIC, AustraliaDepartment of Obstetrics and Gynaecology, Monash University, Clayton, VIC, AustraliaMonash IVF, Richmond, VIC, AustraliaPurpose: To explore in a small pilot study whether oral melatonin, administered during ovarian stimulation increases clinical pregnancy rate (CPR) after IVF and what dose might be most effective.Methods: Pilot double-blind, dose-finding, placebo-controlled randomized clinical trial in private IVF clinics in Australia between September 2014 and September 2016. One hundred and sixty women having their first cycle of IVF or ICSI were randomized to receive placebo (n = 40), melatonin 2 mg (n = 41), melatonin 4 mg (n = 39), or melatonin 8 mg (n = 40) twice per day (BD) during ovarian stimulation. The primary outcome was CPR. Secondary outcomes included serum and follicular fluid (FF) melatonin concentrations, oocyte/embryo quantity/quality, and live birth rate (LBR). Analysis was performed using the intention-to-treat principle.Results: There was no difference in CPR or LBR between any of the four groups (p = 0.5). When all the doses of melatonin were compared as a group with placebo, the CPR was 21.7% for the former and 15.0% for the latter [OR 1.57 (95% CI 0.59, 4.14), p = 0.4]. There were also no differences between the groups in total oocyte number, number of MII oocytes, number of fertilized oocytes, or the number or quality of embryos between the groups. This is despite mean FF melatonin concentration in the highest dose group (8 mg BD) being nine-fold higher compared with placebo (P < 0.001).Conclusion: No significant differences were observed in CPR or oocyte and embryo parameters despite finding a nine-fold increase in FF melatonin concentration. However, this study was not sufficiently powered to assess differences in CPR and therefore, these results should be interpreted with caution. Because this was a small RCT, a beneficial effect of melatonin on IVF pregnancy rates cannot be excluded and merits confirmation in further, larger clinical trials. ANZCTR (http://www.anzctr.org.au/ Project ID: ACTRN12613001317785).https://www.frontiersin.org/article/10.3389/fendo.2018.00545/fullmelatoninAssisted Reproductive TechnologyARTin-vitro fertilizationIVFclinical pregnancy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shavi Fernando Shavi Fernando Euan Morrison Wallace Euan Morrison Wallace Beverley Vollenhoven Beverley Vollenhoven Nicholas Lolatgis Nicole Hope Melissa Wong Mark Lawrence Anthony Lawrence Chris Russell Kenneth Leong Philip Thomas Luk Rombauts Luk Rombauts |
spellingShingle |
Shavi Fernando Shavi Fernando Euan Morrison Wallace Euan Morrison Wallace Beverley Vollenhoven Beverley Vollenhoven Nicholas Lolatgis Nicole Hope Melissa Wong Mark Lawrence Anthony Lawrence Chris Russell Kenneth Leong Philip Thomas Luk Rombauts Luk Rombauts Melatonin in Assisted Reproductive Technology: A Pilot Double-Blind Randomized Placebo-Controlled Clinical Trial Frontiers in Endocrinology melatonin Assisted Reproductive Technology ART in-vitro fertilization IVF clinical pregnancy |
author_facet |
Shavi Fernando Shavi Fernando Euan Morrison Wallace Euan Morrison Wallace Beverley Vollenhoven Beverley Vollenhoven Nicholas Lolatgis Nicole Hope Melissa Wong Mark Lawrence Anthony Lawrence Chris Russell Kenneth Leong Philip Thomas Luk Rombauts Luk Rombauts |
author_sort |
Shavi Fernando |
title |
Melatonin in Assisted Reproductive Technology: A Pilot Double-Blind Randomized Placebo-Controlled Clinical Trial |
title_short |
Melatonin in Assisted Reproductive Technology: A Pilot Double-Blind Randomized Placebo-Controlled Clinical Trial |
title_full |
Melatonin in Assisted Reproductive Technology: A Pilot Double-Blind Randomized Placebo-Controlled Clinical Trial |
title_fullStr |
Melatonin in Assisted Reproductive Technology: A Pilot Double-Blind Randomized Placebo-Controlled Clinical Trial |
title_full_unstemmed |
Melatonin in Assisted Reproductive Technology: A Pilot Double-Blind Randomized Placebo-Controlled Clinical Trial |
title_sort |
melatonin in assisted reproductive technology: a pilot double-blind randomized placebo-controlled clinical trial |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Endocrinology |
issn |
1664-2392 |
publishDate |
2018-09-01 |
description |
Purpose: To explore in a small pilot study whether oral melatonin, administered during ovarian stimulation increases clinical pregnancy rate (CPR) after IVF and what dose might be most effective.Methods: Pilot double-blind, dose-finding, placebo-controlled randomized clinical trial in private IVF clinics in Australia between September 2014 and September 2016. One hundred and sixty women having their first cycle of IVF or ICSI were randomized to receive placebo (n = 40), melatonin 2 mg (n = 41), melatonin 4 mg (n = 39), or melatonin 8 mg (n = 40) twice per day (BD) during ovarian stimulation. The primary outcome was CPR. Secondary outcomes included serum and follicular fluid (FF) melatonin concentrations, oocyte/embryo quantity/quality, and live birth rate (LBR). Analysis was performed using the intention-to-treat principle.Results: There was no difference in CPR or LBR between any of the four groups (p = 0.5). When all the doses of melatonin were compared as a group with placebo, the CPR was 21.7% for the former and 15.0% for the latter [OR 1.57 (95% CI 0.59, 4.14), p = 0.4]. There were also no differences between the groups in total oocyte number, number of MII oocytes, number of fertilized oocytes, or the number or quality of embryos between the groups. This is despite mean FF melatonin concentration in the highest dose group (8 mg BD) being nine-fold higher compared with placebo (P < 0.001).Conclusion: No significant differences were observed in CPR or oocyte and embryo parameters despite finding a nine-fold increase in FF melatonin concentration. However, this study was not sufficiently powered to assess differences in CPR and therefore, these results should be interpreted with caution. Because this was a small RCT, a beneficial effect of melatonin on IVF pregnancy rates cannot be excluded and merits confirmation in further, larger clinical trials. ANZCTR (http://www.anzctr.org.au/ Project ID: ACTRN12613001317785). |
topic |
melatonin Assisted Reproductive Technology ART in-vitro fertilization IVF clinical pregnancy |
url |
https://www.frontiersin.org/article/10.3389/fendo.2018.00545/full |
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