Coping with Oxidative Stress in Reproductive Pathophysiology and Assisted Reproduction: Melatonin as an Emerging Therapeutical Tool.

Cosme P, Rodríguez AB, Garrido M, Espino J. Coping with Oxidative Stress in Reproductive Pathophysiology and Assisted Reproduction: Melatonin as an Emerging Therapeutical Tool. Antioxidants (Basel). 2022 Dec 30;12(1):86. doi: 10.3390/antiox12010086.

Overview

This narrative review summarizes the literature findings regarding the importance of melatonin in reproductive pathophysiology and its potential use in assisted reproductive techniques to improve fertility outcomes. With the current data available, the authors concluded that both animal research and clinical trials provide evidence that melatonin supplementation supports increased fertility success by aiding in reducing oxidative stress. 

Our comments/takeaway from the article

Infertility is a growing concern worldwide, with approximately 16% of couples being impacted. With multiple factors that can affect fertility, from hormonal imbalances to environmental factors, the function of melatonin as an antioxidant has become of interest as a possible therapeutic tool and a supplement we have been recommending for years as part of our fertility protocol. 

This narrative review has provided a comprehensive summary on the multitude of ways melatonin is beneficial for fertility, whether conceiving naturally or using assisted reproductive techniques, with key points that can be shared with patients in a clinical setting. Additionally, for women with endometriosis or PCOS, a dose of 3 mg melatonin per day has been demonstrated to improve multiple aspects of hormonal health that may improve fertility outcomes.  In clinical practice, our team has used 5 mg of melatonin for PCOS. 

Article summary

This article provides a comprehensive summary of melatonin's antioxidant properties on reproductive physiology (Table 1), melatonin application in assisted reproductive techniques (ART) (Image 1, Image 2 & Table 2), and the impact of melatonin on reproductive organs pathophysiology. (Image 3)

Melatonin Application in Assisted Reproductive Techniques (ART)

There is an increased production of reactive oxygen species (ROS) and the risk of oxidative stress, when undergoing ART. Image 1 illustrates the multiple sources of ROS. (Note: in the manuscript this is labeled Figure 2).​

Image 1: Sources of reactive oxygen species (ROS) (Original work Figure 2)​

Image Credit: Cosme P, Rodríguez AB, Garrido M, Espino J. Coping with Oxidative Stress in Reproductive Pathophysiology and Assisted Reproduction: Melatonin as an Emerging Therapeutical Tool. Antioxidants (Basel). 2022 Dec 30;12(1):86. doi: 10.3390/antiox12010086. https://creativecommons.org/licenses/by/4.0/.

Research has focused on the application of antioxidants, particularly melatonin, to reduce oxidative stress due to its free radical scavenging properties.

Image 2: Benefits of melatonin in ART (Originial Work Figure 3)​

Image Credit: Cosme P, Rodríguez AB, Garrido M, Espino J. Coping with Oxidative Stress in Reproductive Pathophysiology and Assisted Reproduction: Melatonin as an Emerging Therapeutical Tool. Antioxidants (Basel). 2022 Dec 30;12(1):86. doi: 10.3390/antiox12010086. https://creativecommons.org/licenses/by/4.0/.

Further, the authors explored the impact of melatonin on reproductive organ pathophysiology, including endometriosis, PCOS and ovarian cancer, which was summarized in Table 1 of the original article.​

Image 3: Melatonin clinical trials on ovarian pathologies (Original Table 1)

​Image Credit: Cosme P, Rodríguez AB, Garrido M, Espino J. Coping with Oxidative Stress in Reproductive Pathophysiology and Assisted Reproduction: Melatonin as an Emerging Therapeutical Tool. Antioxidants (Basel). 2022 Dec 30;12(1):86. doi: 10.3390/antiox12010086. https://creativecommons.org/licenses/by/4.0/.

Limitations noted by AuthorsLack of consistent dose and timing of melatonin used in the studies included. 

Other limitations in our reviewOnce fertilization is achieved, maintaining the pregnancy is as equally important.  Melatonin may support a successful pregnancy. 

Article review completed by Kim Ross, DCN

Content reviewed by Deanna Minich,PhD

January 30, 2023