Melatonin’s Effect on Egg Quality and Fertility

Melatonin is well known as a ‘sleep hormone’ and often taken as a supplement to help improve sleep quality.  But, less familiar, is melatonin's role in fertility and protecting egg quality.

So how does melatonin help when trying to get pregnant, especially as a woman ages?  Melatonin protects the egg from damage due to free radicals, controls the release of reproductive hormones like LH and FSH, and helps with implantation of the embryo.

Melatonin is produced at night:

We all know that sleep is important – just think about how awful you feel the next day after a sleepless night or two.

But what is going on ‘behind the scenes’ in the body at night is also foundational to your health.

You may have heard of the term circadian rhythm, which is applied to all types of functions in the body that go on in a cyclical fashion over the course of the day.

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The obvious examples are your sleep/wake cycle and how your body temperature rises and falls over the course of the day.

Scientists, though, have recently found that about 40% of the molecules produced in your body rise or fall over the course of the day, governed by your circadian clock system. (study)

A big part of this core circadian clock is melatonin, which is produced in the pineal gland, located in your brain. Melatonin levels rise at night (starting around 9pm) and then quickly drops in the morning, as exposure to light causes the production of the molecule to stop.

Not only does melatonin encourage sleep by signaling to other molecules in the brain, but it also regulates other hormonal rhythms as well as acting within the cell as an antioxidant.

How is melatonin important in fertility?

In addition to promoting sleep, melatonin acts in a number of ways to help the reproductive cycle.

In a nutshell, melatonin:

  • Acts as an antioxidant within the egg cell, improving egg quality.
  • Acts as a signaling molecule in the brain, controlling reproductive hormone rhythm.
  • Acts within the uterus, protecting the embryo and facilitating implantation.

Melatonin as an antioxidant:

Egg quality is vitally important, especially as you age.

One main factor affecting your egg quality is the production of reactive oxygen species (ROS) within the egg, specifically within the mitochondria of the egg cell.

This buildup of ROS is called oxidative stress and is a natural byproduct of aging so can't be avoided.  But significant increases in ROS is often due to environmental toxins like poor quality food, harmful lifestyle choices, chronic stress - basically, living in a modern day society.

Several antioxidants protect your cells from the effects of ROS.

One of the most important and potent your body produces naturally is melatonin.

Melatonin is found at higher levels within the ovaries and the egg follicle as compared to the rest of the body.  It acts as an antioxidant there to neutralize the damage from excess ROS. (study)( study)

Melatonin is a unique hormone in that it can pass easily through the outer membrane of the mitochondria, the power plant of the cell.

In addition to acting directly as an antioxidant within the mitochondria, melatonin also stimulates the body to create other natural antioxidants such as glutathione, catalase, and superoxide dismutase (SOD). These antioxidants work together to protect the cell’s nuclear DNA from damage (so important for egg cells!) as well as protecting other parts of the cell. (study)(study)

Not only can melatonin protect eggs from oxidative stress, it may actually speed the growth and maturation of ovarian follicles, according to promising preliminary animal studies. (study)

Melatonin and Ovulation:

The reproductive hormone cycles are both intricate and simply amazing.

Women everywhere understand the monthly cycling of hormone levels involved in menstruation.

Your reproductive hormones also have a daily rhythm, rising and falling in concert over the course of 24 hours.

Recent studies have shown that melatonin regulates gonadotropin-releasing hormone (GnRH), one of the key players in your reproductive hormones. (study)(study) GnRH, in turn, is in control of luteinizing hormone (LH) and follicular stimulating hormone (FSH), both of which are vital to ovulation.

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Your hormones need to rise and fall at the right levels and the right time – like an orchestra playing a complicated sonata. The conductor of this orchestra is GnRH, with melatonin in the drum section helping with the tempo; LH and FSH are important soloists, coming in at just the right time.

Melatonin in implantation:

Within a successful reproductive cycle, a good quality egg matures, released from the ovary during ovulation, fertilizes, and finally, implants into the uterine.

Melatonin is important in all of this – including implantation.

Invader alert!  Your body needs to down-regulate the local immune system, so that you don’t react to the embryo as foreign, and your body also needs to increase certain proteins that are important for implantation in the uterine wall. Melatonin actually helps to make both of those activities take place.  (study)(study)

How is melatonin made?

Melatonin is secreted mainly by the pineal gland. Serotonin, a neurotransmitter, is converted into melatonin via a couple of steps, one of which includes adding a methyl group.  A methyl group is a small molecule made of one carbon surrounded by three hydrogen atoms. This ties back to your need for folate during conception in order to have enough methyl groups.

When light (specifically light in the blue wavelength) hits your eye, it causes a signal to be sent to the brain that suppresses melatonin. Thus during the day, your body has very low levels of melatonin. At night, melatonin levels begin to rise again around sunset. Your melatonin levels normally peak in the middle of your sleep cycle.

Studies on supplementing with melatonin for fertility:

There have been several recent studies and clinical trials using melatonin for increasing fertility.

  • Women with PCOS who struggled with fertility participated in a 6 month trial with supplemental melatonin. The results showed that melatonin regulated the reproductive hormones (FSH, anti-Mullerian, and androgens) and restored the menstrual cycle for many of the women. (study)
  • A study of over 100 women undergoing IVF found that 3 mg of melatonin each night increased fertilization rates by 30%. (study)
  • A large IVF trial in women with PCOS found that a combination of melatonin and myo-inositol increased in-vitro fertilization rates. (study)
  • Not all trials have shown a statistically significant outcome, though. A recent trial in Australia found that while women taking melatonin during IVF trended towards higher pregnancy rates, the effect wasn’t large enough to be statistically significant. (study)

Studies on melatonin as a sleep supplement have very mixed results. One study specifically looked at using melatonin for women with both sleep problems and fertility issues. The results showed that the women supplementing with melatonin had better results for egg retrieval in IVF, but they didn’t have much improvement with their sleep problems. (study)(study)

Supplemental Melatonin:

Melatonin is available over-the-counter in several forms: tablets, gummies, liquid, fast-melts, and timed-release capsules. Melatonin is quickly absorbed and raises serum levels to a peak within one to two hours of taking it. (study)

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The timed-release formulations better mimic natural melatonin levels and sustain the levels over the course of the night so is recommended, especially if you have difficulties sleeping.

While most of the trials for fertility used doses of 3 mg/night, people tolerate melatonin supplements differently, and some report side effects of headaches, slight nausea, or grogginess after taking too much melatonin. So this may be something that you want to try first on a weekend, and you may need to try several different doses to find the right fit for your body.

Why are your melatonin levels low?

Light in the morning is your body’s signal to turn off the melatonin production. Similarly, light in the blue wavelengths at night also suppresses the rise of melatonin levels.

Throughout human history, the only light at night was from the moon and from fire (torches, candles, oil lanterns, etc.) Light from a fire has little to no blue wavelengths, and thus it has very little to no impact on melatonin levels.

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Fast-forward to our modern era of watching TV while simultaneously surfing smartphones in the evening. Everything with a screen gives off lots of light in the blue wavelengths.  To make it worse, the new energy-saving LED lightbulbs are also full of light in the blue spectrum.

Genetics and Melatonin:

Melatonin is made in the body by converting serotonin to melatonin. Most people don’t have a genetic problem producing melatonin, rather the production is limited more by environmental factors such as light.

Like most hormones, melatonin is a molecular signal, and it interacts with melatonin receptors in the cell.

Genetic variants of those receptors can cause a decrease in how well they function, thus impacting how much melatonin is needed in the body.

MTNR1B is the gene coding for one of the melatonin receptors. Changes to this gene have been linked to an increased risk for diabetes and gestational diabetes, as well as an increase in insulin resistance in women with PCOS. (study)(study) This is due to the action of melatonin in regulating insulin levels at night.

The MTNR1B variant is an excellent example of how understanding your genetic variants can help you bypass the problems they can cause. Studies have shown that people with this variant are at a much higher risk of diabetes – but only if they eat dinner later at night. Simply moving their evening meal to an earlier time can completely prevent the increase in diabetes risk. (study)

Check your genetic data for rs10830963:

  • GG: linked to higher risk of diabetes, increased fasting glucose – don’t eat dinner late
  • CG: linked to higher risk of diabetes, increased fasting glucose – don’t eat dinner late
  • CC: normal MTNR1B variant

Another melatonin receptor, MTNR1A, is important in IVF. It is specifically found in the egg cell and also upregulated in the uterus for implantation. (study)(study)(study)

Variants in the MTNR1A gene have been linked to being more susceptible to exhaustion and sleep disturbance when staying up late or working the late shift. The researchers believe this was due to the variant causing fewer melatonin receptors and a greater impact from light at night. (study)

Check your genetic data for rs12506228:

  • AA: likely fewer melatonin receptors in the brain, a greater impact from light at night
  • AC: somewhat fewer melatonin receptors, somewhat greater impact from light at night
  • CC: normal MTNR1A variant

This is all newly emerging research on how genetic variants in the melatonin receptors impact an individual’s need for melatonin. New discoveries on the topic are coming out all the time, but at this point, few variants have been found that decrease your need for melatonin. So your best bet is to assume that melatonin is important for your health and your fertility.

How can you raise your melatonin levels naturally?

Blocking out blue light at night will raise your natural production of melatonin. There are a couple of ways to do this:

  • Shut off your electronics two hours before bed and turn off the bright overhead lights. Then you can use low watt lamps with either incandescent bulbs or the antique-looking Edison bulbs. You could read a book (a real book, not from a back-lit e-reader), take up a hobby, relax in the bathtub, listen to music, or enjoy some conversation time with family and friends. (study)
  • Alternatively, there are blue-blocking glasses available that block 100% of blue wavelengths (orange colored lenses)

How much will blocking out blue light at night actually boost your melatonin levels? A study of people using blue light blocking glasses for three hours before bed found that their melatonin levels rose an average of 50% over the course of wearing the glasses at night for a week. Other studies have shown that wearing the orange lensed glasses increases sleep quality and helps people fall asleep faster. (study)(study)

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The flip side of blocking out light at night is that you need bright light during the daytime. Getting outside, or at least exposing yourself to the brightest possible indoor lighting, will help to shut down melatonin during the day and also increase melatonin levels at night. (study)

The advantage to raising your melatonin levels naturally is that it increases the levels at the right time of the night. The disadvantage is that it is socially awkward to go around wearing orange glasses at night!

You may find that your best bet is a combination of all three ways of raising melatonin:

  • blocking blue light at night when you can
  • adding supplemental melatonin at the level that is right for you
  • getting sunlight during the day

What about your male partner? Is melatonin important for sperm?

The antioxidant properties of melatonin make it very important for sperm quality. We are all exposed every day to various chemicals and heavy metals through our food and environment. Melatonin can help lessen the damage to sperm from these compounds.

  • In sperm samples, melatonin was found to protect the sperm from impacts of mercury exposure. (study)
  • Melatonin was also found to protect sperm against the damage from organophosphorus pesticides. (study)
  • BPA, commonly found in plastics, has been shown to damage sperm DNA. Melatonin can protect the sperm from BPA-induced changes to the DNA. (study)(study)

Wrapping up and recapping:

Timing is everything when it comes to getting pregnant. At the heart of your body’s timing mechanism is melatonin.

Melatonin is foundational for a healthy pregnancy. It acts as an important antioxidant to improve egg and sperm quality.  It  also regulates the hormones needed for ovulation and then implantation. Melatonin is naturally produced by the body at night, and exposure to light at night decreases your melatonin production. Supplemental melatonin has been shown to improve in vitro fertilization rate.