Melatonin is a hormone produced naturally in the body. Its primary function it to regulate the body’s sleep and wake cycles (circadian rhythm). Melatonin also has antioxidant properties; it is involved in neutralising oxidative stress caused by normal cell processes and inflammation.
Oxidative stress can play a role in infertility by impacting egg quality and therefore reducing the maturation of eggs and fertilisation rates. There is some evidence to suggest that melatonin supplements may help to further neutralise oxidative stress.
Why is it used in assisted reproductive technology (ART)?
During the stimulation phase of IVF/ICSI, oocytes (eggs) and embryos may be exposed to more oxidative stress and cause damage to cell structures. It is theorised that supplemental melatonin may help to neutralise the by-products of oxidative stress leading to improved fertilisation results and implantation rates.
What is the evidence?
A systematic review and meta-analysis of randomised trials in China (Hui et al. 2020) suggests that melatonin significantly increases the clinical pregnancy rates in assisted reproductive technology (ART) cycles. It also suggests alink between melatonin levels and an increase in the number of eggs collected, the number of mature eggs collected and the number of good quality embryos formed. There was not significant evidence to suggest that melatonin increases live birth rate - further large scale studies are required to confirm this.
Does melatonin have any side-effects?
Melatonin is generally well tolerated with few side-effects. Common side effects include fatigue during the day, dizziness, headaches, nausea and vivid dreams. Less commonly experienced side-effects include abdominal discomfort, anxiety and short-lasting feelings of depression. Melatonin can interact with other medications and it is therefore important to disclose any other medications being taken.
Melatonin in conjunction with Myo-Inositol (MI)?
Recently, studies on inositol supplementation during IVF have gained particular importance due to the effect of this molecule on reducing insulin resistance, improving ovarian function, oocyte quality and embryo and pregnancy rates and reducing gonadotropin amount during stimulation. Inositol and its isoform, especially myo-inositol (MI), find their application as pre-stimulation therapy in polycystic ovary syndrome (PCOS) patients undergoing IVF cycle and, recently, also in all kinds of infertile patients such as poor responders. Using melatonin in conjunction with MI has been suggested to improve egg and embryo quality, particularly those with PCOS. More large scale studies are required to gain further statistical significance.
Side effects of MI?
The general consensus seems to be that myo-inositol is a safe supplement to take given no clinically relevant adverse effects have been found in several human studies that looked at doses of 4000 mg per day throughout pregnancy.
Hui, K-L, Ye, X, Wang, S & Zhang, D, 2020. ‘Melatonin application in assisted reproduction technology: A systematic review and meta-analysis of randomized trials’, Frontiers in Endocrinology, vol. 11, article 160. Vitale, S, Rosetti, P, Corrado, F, Rapisada, A, La Vignera, S, Condroelli, R, Valenti, G, Sapia, F, Lagana A, Buscema, M, 2016. ‘How to achieve high-quality oocytes? The key role of myo-inositol and melatonin’, International Journal or Endocrinology, http://dx.doi.org/10.1155/2016/4987436