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.

Highlights

  • Infertility is considered as failure to conceive after a year or more of frequent unprotected sexual intercourse [1]

  • AMT6s concentrations increased by several folds (p < 0.05) in those unexplained infertility (UI) patients who were given 3 mg or 6 mg melatonin/day for 40 days (Figure 1A), indicating that a single daily dose of melatonin was enough to raise systemic concentrations of the indoleamine

  • We provided evidence that melatonin supplementation: (i) Positively impacted on the oxidative balance in the follicular fluid (FF) of women with UI since it is capable of restoring concentrations of diverse markers of oxidative status to levels found in fertile women; (ii) improved oocyte quality and, the amount of transferable embryos in UI

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Summary

Introduction

Infertility is considered as failure to conceive after a year or more of frequent unprotected sexual intercourse [1]. Infertility is said to be unexplained when common causes of infertility, such as absent ovulation and poor semen quality or tubal pathology, have been excluded after the completion of standard fertility tests [2]. Causes of idiopathic infertility are currently unknown, factors, such as a perturbed oxidative balance, may affect women fertility. An overabundance of reactive oxygen species (ROS) in the follicular fluid (FF) of women with idiopathic infertility has been reported [3]. Other authors have found low levels of antioxidants in the FF of women undergoing evaluation for idiopathic infertility [4]. It is worth noting that embryo quality and oocyte maturation are negatively correlated with high levels of ROS in the FF of infertile women [5,6]

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