Skip to main content
Melatonin and fertility

Melatonin and Fertility: Does Melatonin Affect Fertility?

Melatonin and fertility have a surprising connection! When you think of melatonin, you think of sleep, right? Well, melatonin actually has other benefits besides aiding sleep. That includes improving cognitive function and even fertility!

Here’s the gist of it in a single paragraph:

Melatonin is a powerful free radical scavenger and protects the oocyte from oxidative stress, especially at the time of ovulation. The cyclic levels of melatonin in the blood pass through the placenta and aid in the organization of the fetal SCN. In the absence of this synchronizing effect, the offspring may exhibit neurobehavioral deficits. Also, melatonin protects the developing fetus from oxidative stress. Melatonin produced in the placenta likewise may preserve the optimal function of this organ.

1. Melatonin Improves IVF-ET Outcomes by Enhancing Oocyte Quality

Does melatonin affect fertility? Let us explain the connection of melatonin and fertility to you. Melatonin treatment significantly increases the number of oocyte collected, mature oocyte, and good quality embryo, as supported by a medical study.

Melatonin acts an assassin, hunting for enemies that may potentially harm your eggs. How exactly?

Melatonin is a free radical scavenger. It neutralises reactive oxygen species (ROS) in your uterus. ROS levels increase especially when its time for your eggs to start maturing.

This is due to an increase in luteinising hormone at the start of the luteal phase (around day 13) — involved in the final maturation and release of the matured oocyte from the ovarian follicle — which stimulates increased mitochondrial function in oocytes, to produce more energy in the form of ATP molecules. The ATP molecules are used to promote the growth and maturation of the oocyte.

However, with increased metabolic rate, there is a higher chance of electron leakage from the electron transport chain in the mitochondria. This forms ROS.

Excessive ROS can oxidise and modify essential enzymes and proteins in the oocyte, disrupting their function. ROS can interact with lipids through lipid peroxidation and cause the oocyte phospholipid membrane to lose its integrity and even rupture.

Additionally, DNA in the oocyte can be damaged by ROS, signalling apoptosis, where the oocyte “commits cell suicide”. All these processes inhibit the proper growth and maturation of the oocyte.

But fret not, melatonin detects and destroys these ROS and protects your eggs from such harm.

Moreover, melatonin’s antioxidant properties allow the delay of ovarian ageing (decrease in number and quality of oocytes). By neutralising ROS, melatonin stops the telomeres of the mitochondrial DNA from shortening, preserving the proper function of the egg’s mitochondria. Mitigating ovarian ageing is crucial in ensuring optimal reproductive health and successful conception.

Additionally, when the sperm is added to the egg during IVF, the sperm also benefits from the presence of melatonin in the culture media! Melatonin’s ROS scavenging abilities help enhance motility of sperm cells, enabling them to penetrate the oocyte membrane faster.

High-quality oocytes are essential for successful fertilisation, to produce high-quality embryos.

Melatonin can also be injected directly into cultures to promote healthy cell proliferation in the embryo stage.

2. Melatonin aids embryonic implantation and fetal development

This part of melatonin and fertility explanation gets a bit science-y and you may want to skip to the TLDR part. Nevertheless, continue reading if you’re curious.

Melatonin also promotes the formation of blastocysts during embryonic development, which is crucial for implantation.

The blastocyst is characterised by two cell types: inner cell mass and the outer layer of cells called the trophoblast layer. Let’s focus on the trophoblast layer for now.

The trophoblast cells release enzymes that facilitate penetration of the trophoblast into the endometrial lining. This promotes formation of the chorionic villi and the placenta, which are both crucial in the exchange of nutrients, oxygen and waste products between the developing embryo and maternal blood. ROS can disrupt such processes, but thankfully melatonin can block ROS action.

Melatonin and Fertility: Warning!

Trophoblast cells are extremely sensitive to oxygen levels, which fluctuate during pregnancy. These fluctuations cause hypoxia-reoxygenation (H/R) to occur. Basically, hypoxia = low oxygen levels, whereas reoxygenation = restoration of normal levels of oxygen. Hypoxia during pregnancy can result from factors such as placental insufficiency, umbilical cord issues, maternal respiratory conditions, anemia, cardiovascular problems, high altitude, smoking, and multiple pregnancies, potentially affecting fetal oxygen supply and development.

Typically, the trophoblast cells are equipped with mechanisms to restore the normal oxygen levels.

Reoxygenation causes increased formation of ROS. This puts the trophoblast cells at risk of H/R induced oxidative damage. This activates a pathway involving Bax and Bcl-2 proteins in the mitochondria. Bax promotes apoptosis while Bcl-2 inhibits it.

Under oxidative stress, the balance shifts in favor of Bax, leading to dysfunctional mitochondria, which release cytochrome c. This promotes formation of apoptosomes that result in DNA fragmentation. This in turn signals for cell death. This process, if occurring excessively, may contribute to fetal tissue damage.

Thankfully, melatonin binds to the MT1 and MT2 receptors on trophoblast cells. As a hunter of ROS, melatonin is thus able to prevent H/R induced oxidative stress and subsequent cell death.

TLDR: Melatonin can pass from the maternal blood into the fetal blood across the placenta, bind to receptors on the cells of the embryo and prevent them from being damaged by ROS.

3. Melatonin combats unexplained infertility

It is reported that women with infertility issues have an abundance of ROS in their follicular fluid, thus impacting the release of mature oocytes from their ovaries.

Given the intricate role of oxidative stress, as highlighted in the content above, it may be worthwhile for women facing fertility challenges to explore the potential benefits of melatonin supplements, known for their antioxidant properties.

It now seems like melatonin is a god-send drug. But, it may prevent ovulation.

Now, we will delve deeper to understand the relationship between melatonin and fertility, which, as it turns out, has its own associated risks.

How does ovulation happen?

  • The pituitary gland in the brain secretes follicle stimulating hormone (FSH), which stimulates the growth and maturation of ovarian follicles.
  • This results in the development of a mature egg which produces estrogen.
  • Estrogen, in addition to causing the uterine lining to thicken in preparation for embryo implantation, stimulates the release of luteinising hormone (LH) from the ovaries.
  • LH spurs ovulation by triggering the release of a mature egg from the ovary.

How does melatonin mess it up?

  • Melatonin will bind to the MT1 and MT2 receptors on the neurons in the hypothalamus that release gonadotropins (GnRH).
  • This inhibits the neurons from secreting GnRH, and reduced GnRH levels cause the pituitary gland to secrete less LH and FSH.
  • If LH is under-secreted, ovulation may not happen as it usually would.

It is advised that women who are trying to get pregnant naturally without IVF should avoid taking exogenous melatonin during the follicular phase (day 1 to 12) of their menstrual cycle. Rest assured, this only occurs in instances where the dosage is excessively high, especially when combined with exogenous progesterone.

When to take melatonin for fertility? How long to take melatonin for fertility?

Without IVF (Natural Conception)

To fully benefit from melatonin’s ROS scavenging abilities, aim to take melatonin during the LH surge phase (as mentioned in point 1 of this article), that is around day 13, right before ovulation. Avoid taking melatonin during day 1 to 12 as that is during the follicular phase.

Melatonin supplementation can be continued during the luteal phase, as it can stimulate progesterone production and stabilise the corpus luteum.

Most fertility clinics prescribe 2-10 mg of melatonin each night for women experiencing infertility issues. A study also showed that a group of women who took 6 mg of melatonin each night for 40 days, one hour before bed, showed higher levels of mature oocytes being released.

With IVF

Typically, melatonin supplementation can be taken on day 2 or 3 of the menstrual cycle, to prepare for IVF. A study showed that 3-6 mg of melatonin a day was given to patients with unexplained infertility undergoing fertility aid. This helped to control ovarian stimulation until the day of follicular puncture (egg retrieval).

Why is it that with IVF, melatonin can be taken so early? Our hypothesis is that melatonin’s benefits on improving oocyte quality over-ride the minor disruption it may cause on ovulation. This is because ovulation is already managed by IVF procedures and other medications e.g. GnRH analogs or other drugs that facilitate superovulation.

Melatonin for IVF When to Stop?

If you are doing a fresh cycle transfer, it makes sense to continue using melatonin, for the same reasons melatonin is used during the luteal phase or 2 week wait (2ww).

If you have finished your retrieval and are waiting for the next FET, it still makes sense to continue using melatonin.

Hence, it makes sense not to stop using melatonin if you are on an IVF cycle. That said, melatonin use should be controlled when trying naturally.

Details for nerds:

  • Clomiphene citrate is a selective estrogen receptor modulator (SERM). It works by blocking estrogen receptors in the hypothalamus.
  • The hypothalamus normally produces GnRH, which signals the pituitary gland to release follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
  • By blocking estrogen receptors in the hypothalamus, clomiphene citrate disrupts the negative feedback mechanism that estrogen typically exerts. This results in an increase in GnRH secretion, which, in turn, stimulates the pituitary gland to release more FSH and LH.
  • Clomiphene citrate is usually taken orally for a specific duration of the menstrual cycle, often starting on day 3 or 5 and continuing for several days.
  • Ovulation is typically expected around 5 to 10 days after the last dose of clomiphene citrate.

Additionally, during IVF-ET therapy, FSH is administered. However, there’s a risk of premature ovulation due to a surge in LH. To prevent this, GnRH analogs, either agonists (e.g., leuprolide) or antagonists (e.g., ganirelix), are used. GnRH agonists initially cause an LH surge but then downregulate GnRH receptors, while antagonists rapidly block these receptors.

This careful hormonal control, monitored through ultrasound and hormone levels, prevents premature ovulation, ensuring optimal timing for egg retrieval. The retrieved eggs are then fertilized in the laboratory, and resulting embryos are transferred to the uterus, increasing the chances of successful IVF-ET.

After IVF-ET, melatonin can be taken to promote implantation as well as early fetal development.

Hence, melatonin is often administered early in the menstrual cycle in the context of IVF, even before ovulation, potentially capitalise on its benefits in improving egg quality. Melatonin can be taken as an “oocyte quality booster/oocyte guardian” during IVF. 

Should I combine melatonin with other drugs to increase my chances of fertility?

Yes. Adding myo-inositol along with melatonin, may improve fertility even more than with melatonin alone. Myo-inositol has been demonstrated to be important for egg quality, ovulation, and hormone balance in women with PCOS.

Myo-inositol is a naturally occurring sugar alcohol with insulin-sensitising properties. Insulin sensitivity is crucial for the proper utilisation of insulin by cells, particularly in tissues like the ovaries. In conditions such as PCOS, insulin resistance is common, leading to hormonal imbalances and disrupted reproductive function.

Insulin resistance is commonly observed in women with PCOS. Elevated insulin levels can stimulate the ovaries to produce excess androgens (male hormones) and inhibit the release of eggs during ovulation.

And that’s not all. Women with insulin resistance may respond less favorably to IVF! Thus, by taking myo-inositol, insulin resistance enhanced, leading to an improve the chances of success with fertility interventions.

So you can think of myo-inositol as a teacher that prepares you for an “exam” (referring to IVF), and melatonin as a cheat sheet during the “exam”.

Of course, as with any other drug, do consult your doctor so that they can designate a customised dosage plan for you.

Can you take melatonin while conceiving?

No, melatonin is mainly used to protect the oocyte and embryo from oxidative stress and promote healthy formation of placenta. Since melatonin can pass from maternal blood to fetal blood across the placenta, it may potentially disrupt the fetal circadian rhythm and affect middle/late-stage fetal development.

This is because the fetal circadian rhythm is closely linked to early fetal neurodevelopment. Circadian rhythms influence the release of neurotransmitters, hormones, and growth factors. Proper synchronisation of these biochemical signals is crucial for the formation and maintenance of neural connections, which is essential for normal brain function.

We hope this melatonin and fertility article has helped you in your journey towards a healthy and successful pregnancy. Melatonin appears to have multifaceted benefits in the realm of fertility, IVF-ET, and early fetal development, with antioxidant properties being a key mechanism. However, caution is advised regarding potential disruptions to ovulation and the fetal circadian rhythm. Note that this article should not take the place of advice from your healthcare provider.

Now, you can say goodbye to the stork and hello to melatonin for fertility, the new baby deliverer.

How can we help? Fill up form to let us know!

This is so we can get back to you on Whatsapp to schedule an appointment.
For communications.
Let us know what you are facing.

We do a fantastic job of assisting you if you are trying to conceive, are pregnant, or experiencing challenges after birth.

Location: 545 Orchard Road #16-03/07 Far East Shopping Centre (next to Wheelock Place) Singapore 238882.
Phone: +65 8809 9396

© Copyright 2023 All Right Reserved Soma Clinic