- What is metformin?
- Does taking metformin help to improve fertility?
- About PCOS
- How does metformin help with fertility in PCOS?
- What are the side effects of metformin?
- Who can take metformin for fertility?
- Who cannot take metformin for fertility?
- How long does metformin take to work for fertility?
Metformin is a popular medication for treating diabetes, but it has many other uses too.
Did you know metformin can be used for fertility?
In this article, we’ll tell you everything you need to know about using metformin for fertility, including how it works, its benefits, side effects, and more.
What is metformin?
Metformin is an oral medication classified under a group of anti-diabetics called biguanide. It is typically taken at least once (extended-release) to several times (immediate-release) a day.
In the United States, metformin is sold under commercial names such as Glucophage, Fortamet, Glumetza, and Riomet. It is widely available in the market, but you can only get it with a doctor’s prescription.
Does taking metformin help to improve fertility?
Yes. Metformin has several therapeutic effects, one of which is improving fertility.
People with polycystic ovarian syndrome (PCOS) might be the second largest population benefiting from metformin treatment, just after diabetes patients.
Although metformin is shown to improve fertility in women with PCOS, it is not used as a first-line or primary treatment. This is because studies have shown clear benefits of another fertility-enhancing medication, clomiphene (Clomid), over metformin.
However, if clomiphene is not working for you, your doctor may recommend using metformin as an alternative to help you get pregnant.
Metformin is especially beneficial for women with PCOS who are overweight because metformin will not cause weight gain.
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Polycystic ovarian syndrome (PCOS) is one of the most common causes of female infertility. In the United States, PCOS affects up to 5 million women of childbearing age.
PCOS impedes the ovaries’ function in producing eggs, causing so-called anovulatory infertility. Due to an absence or very low frequency of ovulation, women with PCOS will experience infrequent or irregular menses.
Plus, as a systemic endocrine disease, the health impacts of PCOS are a lot more than that.
Women with PCOS can also suffer from acne, thinning scalp hair, and excessive hair growth on the face and body. The condition also predisposes women to diabetes at a younger age, usually below 40.
Relationship between PCOS and infertility
Before trying to understand how metformin works in treating PCOS, it is imperative to know why and how PCOS causes infertility. In principle, the mechanism is known as insulin resistance:
- In PCOS patients, the body tissues fail to utilize the insulin produced by the pancreas appropriately. This condition is called insulin resistance.
- Since insulin is not used, blood glucose level remains high. This stimulates the pancreas to keep producing more insulin, causing an insulin overload in the body.
- High levels of insulin negatively impact the ovaries, causing them to produce too much testosterone, a male hormone usually presents in a minimal amount in the female’s body.
- Testosterone interferes with the development of the follicles. Follicle is the home to the female eggs – it is a sac containing and nourishing the eggs. Ovulation is the process where the follicle matures and releases the egg.
- When the follicles are disturbed, fewer or no eggs are released. Hence, there is no ovulation. The woman is then infertile or finds it very difficult to get pregnant.
How does metformin help with fertility in PCOS?
Metformin treats infertility in PCOS by enhancing the body tissues’ sensitivity to insulin, the exact counteraction to the reason for infertility by PCOS (insulin resistance).
Another proposed mechanism is metformin prevents excessive insulin activity in the ovaries, thus reducing its negative impact on ovulation.
Other than fixing PCOS, metformin helps improve fertility by controlling diabetes, one of the most common endocrine disorders closely linked to PCOS.
Metformin exerts positive impacts in treating diabetes by:
- Reducing glucose production in the liver
- Stopping the conversion of glycogen (another form of sugar) and adipose tissue to glucose
- Increasing the uptake of glucose by cells
All the mechanisms above reduce the amount of glucose circulating in the blood circulation, lowering your blood glucose level.
Much evidence from research studies also reports that metformin helps reduce weight gain induced by PCOS, resume menstrual regularity, restarts ovulation, and improve the chance of pregnancy.
What are the side effects of metformin?
Just like any other medication, metformin comes with side effects.
We can broadly classify the side effects of metformin into three groups: common side effects, serious side effects, and long-term side effects.
Common side effects
A side effect is considered common when it happens in more than 1 in 100 people. In the context of metformin, these common side effects include:
- Digestive symptoms, including nausea, vomiting, diarrhea, bloating, stomach pain, indigestion (heartburn), and constipation.
- Systemic symptoms, including loss of appetite, a bitter or unpleasant metallic taste in the mouth, headache, skin flushing, nail changes, and muscle pain.
- Low blood sugar symptoms, including feeling hungry, trembling or shaking, sweating, confusion, and difficulty concentrating.
Severe side effects
Metformin can cause a few severe side effects, but they are extremely rare (about 1 in 10000 people).
These red flags should alarm you to seek medical attention immediately:
- Severe unwell and tiredness
- Rapid breathing or high-pitch breathing sound (wheezing)
- Abnormally fast or slow heartbeat
- Chest tightness or pain
- Yellowish discoloration of the eyes and skin
- Skin rash that may include itchy, red, swollen, blistered, or peeling skin
- Swelling of the mouth, face, lips, tongue, or throat
Long-term side effects
Vitamin B12 deficiency is a well-known side effect of long-term metformin consumption. The exact mechanisms of how chronic metformin intake impacts vitamin B12 levels in human bodies are still not yet fully understood.
One of the highly plausible explanations is metformin impairs the ability of our small intestine to absorb vitamin B12, as proposed by recent research studies.
You should inform your doctor if you experience any symptoms below:
- Extreme tiredness or lethargy
- Muscle weakness
- Sore, red tongue
- Mouth ulcers
- Vision problems
- Changes in skin color (into pale or yellow skin)
Your doctor will likely take some of your blood to check for vitamin B12 levels. You may be prescribed vitamin B12 supplements or injections when necessary.
Who can take metformin for fertility?
Metformin is typically used to improve fertility in women who:
- Have PCOS with insulin resistance, or
- Tried but failed to improve their fertility with conventional fertility treatments such as Clomiphene (Clomid)
Metformin is not used as the first-line treatment for fertility. Your doctor may prescribe metformin in combination with Clomid, Letrozole, or either of these drugs to boost your chances of getting pregnant.
Suppose you are going for in-vitro fertilization (IVF). In that case, your doctor may also recommend metformin to reduce your risk of getting ovarian hyperstimulation syndrome (OSSH), a complication of taking ovulation-stimulating drugs in preparation for IVF.
The symptoms of OSSH can be excruciating. OSSH causes your ovaries to swell, causing abdominal discomfort, bloating, diarrhea, and vomiting.
Who cannot take metformin for fertility?
Metformin is generally regarded as a low-risk, well-tolerated drug. However, people with certain conditions might be prohibited from taking metformin.
Inform your doctor before starting your metformin therapy if you have the following:
- A history of allergic reactions to metformin or any other medication
- Uncontrolled diabetes
- Liver or kidney diseases
- Severe infection
- Heart conditions or had a recent heart attack
- Respiratory disorders or breathing difficulties
Also, tell your doctor if you expect any scans involving a dye injection into your blood or surgery where you will be put to sleep (general anesthesia).
Your doctor might recommend you refrain from drinking too much alcohol while taking metformin, as it can slow down the elimination of the drug from your body, imposing a higher risk of drug overload.
How long does metformin take to work for fertility?
The period it takes to see metformin’s benefits in improving fertility may vary from person to person.
Some women taking metformin for PCOS start to see improvements in their fertility as early as one month after starting metformin, while some take longer. Some women only see its effects after taking metformin for 6 months or more.
There has also yet to be a consensus regarding the optimal duration of metformin therapy in treating infertility. The course of metformin treatment varies across research studies, ranging from 4 weeks to 60 weeks.
Yes. Studies have shown that metformin increases ovulation rate in women with PCOS compared to those who do not take metformin.
Metformin helps with ovulation by improving insulin sensitivity. High levels of insulin have a negative effect on the ovaries, hence preventing ovulation and causing infertility. Metformin has been shown to help promote ovulation and thus improve fertility.
Poor egg quality is often used as a factor for doctors to start their patients on metformin prior to IVF treatments. Hormonal imbalances, stress, and environmental exposure are among the most common causes related to poor egg quality.
Animal studies have shown that metformin improves the quality of oocyte (a developing egg) and embryo development outcomes.
These results may suggest that metformin could reverse the adverse effects of excessive androgen (hyperandrogenism) on oocytes in PCOS individuals.
While there are studies showing that metformin does improve egg quality when used in IVF treatment, there are reports stating that there is no difference in egg quality between those who took metformin and those who did not.
More larger-scale randomized control trials are needed to reach a more convincing conclusion.
There is insufficient evidence to conclude that metformin increases the chance of getting twins.
The chances for twin or multiple pregnancies are higher if the woman has twins in her family and PCOS.
However, studies suggest that the chances of a twin pregnancy among women with PCOS are more likely due to other interventions, such as Clomid intake, rather than the effect of metformin.
Yes. The use of metformin is considered safe for pregnancy, and there are no reported teratogenic effects to date.
The U.S. Food and Drug Administration (FDA) labels metformin as a category B drug. This means there is no evidence of harm in animal studies, but inadequate studies were done on pregnant women.
In vitro laboratory experiments have shown that metformin improves endometrium receptivity in women with PCOS. The higher the receptivity, the more favorable the condition for embryo implantation on the endometrium.
However, there is insufficient literature, especially on animals and clinical studies. More research is needed to provide clarity on this matter.
No. People with type II diabetes, obesity, metabolic syndrome, and certain endocrine conditions can also benefit from taking metformin.
In males, it is widely known that diabetes and obesity affect sperm production, lowering sperm count and sperm quality. All these can lead to infertility. By using metformin to treat these root causes, you can enhance your fertility.
Metformin can improve fertility and your chance of getting pregnant. If you have PCOS associated with insulin resistance, or if you are not responding to clomiphene, your doctor may suggest metformin to improve your fertility.
In addition to using metformin for fertility, a healthy lifestyle, including diet and exercise, can also enhance your fertility and chances of getting pregnant with PCOS.