Impact of Melatonin Supplementation in Women with Unexplained Infertility Undergoing Fertility Treatment

Abstract

Unexplained infertility occurs when common causes for a couple’s inability to conceive have been excluded. Although origins of idiopathic infertility are still unclear, factors, such as an altered oxidative balance, are believed to be involved. Melatonin is an outstanding antioxidant reportedly present in the follicular fluid (FF), which has been suggested as a useful tool in the management of human fertility. Herein, we observed that intrafollicular concentrations of melatonin were blunted in women with unexplained infertility (UI), which was associated with a marked oxidative imbalance in UI patients’ FF. Based on these findings, this randomized pilot study was aimed at assessing whether exogenous melatonin ameliorated oxidative stress and improved in vitro fertilization (IVF) success rates in UI. Thus, 3 mg/day or 6 mg/day of melatonin were given to UI patients for a period spanning from the first appointment to control ovarian stimulation until the day of follicular puncture. Our results indicate that melatonin supplementation, irrespective of the two doses tested, ameliorated intrafollicular oxidative balance and oocyte quality in UI patients, and that this translated into a slight increase in the rate of pregnancies/live births. Therefore, although the indoleamine has shown therapeutic potential in this clinical setting, larger clinical trials in populations with different backgrounds are encouraged to corroborate the usefulness of melatonin.

Melatonin Application in Assisted Reproductive Technology: A Systematic Review and Meta-Analysis of Randomized Trials

“…The PRISMA flow diagram of the review process was presented in Figure 1. A total of 10 randomized trials were included for analysis (18)(19)(20)(21)(22)(23)(24)(25)(26)(27). Characteristics of the included studies were presented in Tables 1, 2.…”

“…Nine studies reported the effect of melatonin on clinical pregnancy in IVF/ICSI-ET cycles (18)(19)(20)(21)(23)(24)(25)(26)(27). Meta-analysis suggested that melatonin treatment significantly increased clinical pregnancy rate [OR = 1.39 (1.05, 1.84), P < 0.05].…”

“…Six in-vivo studies reported the effect of melatonin vs. control on clinical pregnancy (19,(22)(23)(24)(25)27…”

Importance of Melatonin in Assisted Reproductive Technology and Ovarian Aging

“…It is possible that the administration of melatonin to patients suffering from infertility increases follicular concentrations of melatonin, which thereby inhibits oxidative stress and improves the quality of oocytes, thus improving fertilization and pregnancy rates. After this initial study, other reports also examined whether melatonin therapy improves the clinical outcome of IVF-ET, with the findings likewise also showing that the concurrent use of melatonin increases the number of mature oocytes, the fertilization rate, and number of high-quality embryos [39,[46][47][48][49][50] (Table 1). It is suggested that the effects of melatonin include an increased concentration of melatonin in the follicular fluid and a reduced 8-OHdG concentration, which leads to the conclusion that melatonin's multiple antioxidant actions lower oxidative stress in oocytes [39,50].…”

Melatonin and Female Reproduction: An Expanding Universe

“…These intriguing findings are consistent with the view that pharmacological melatonin administration increases intra-follicular melatonin concentrations, reduces intra-follicular oxidative damage and may have a beneficial effect on fertilization and pregnancy rates during ART. In a recent report, similar benefits were found in 40 women with idiopathic infertility who were administered pharmacological melatonin and who subsequently showed improved intrafollicular oxidative capacity and oocyte quality in IVF protocols (58).…”