How Metformin Is Used for Fertility

Metformin is an insulin-sensitizing drug primarily used to treat diabetes, but it can also be used to promote ovulation. Exactly how the medication improves fertility is unclear, but metformin is commonly prescribed to treat various fertility issues.

People who have polycystic ovarian syndrome (PCOS) might benefit from taking metformin alone, with Clomid, or during IVF treatment. Studies show that taking the drug in combination with other treatments like Clomid typically produces better results than using it on its own.

While metformin can be used for the treatment of infertility, it is not technically a fertility drug. When taken to treat infertility, it is considered an off-label use (which means that pregnancy achievement is not the original purpose of the drug). Learn more about using metformin for PCOS and getting pregnant.

How Metformin Is Used for Fertility

To understand what taking metformin for fertility does, it helps to understand insulin resistance and what insulin does in the body. Many people with PCOS have insulin resistance. If the body's cells stop reacting to normal levels of insulin and instead become less sensitive (or resistant) to it, this is called insulin resistance.

When the cells become resistant, the body thinks that there is not enough insulin and triggers the production of more insulin (in excess of what the body needs). Insulin is critical to the absorption of sugar (which becomes energy) into the body's cells and keeping the right level of insulin in the bloodstream is important for overall health.

There seems to be a connection between insulin and reproductive hormones. It's not clear exactly how the two are connected, but increased insulin levels seem to lead to increased levels of androgens. While people of either biological sex have androgens, they are typically thought of as "male hormones." High androgen levels in females can lead to PCOS symptoms and problems with ovulation.

Metformin and other insulin-sensitizing medications (such as rosiglitazone and pioglitazone) lower excess levels of insulin in the body and can be used to treat PCOS.

Metformin for PCOS

There are several reasons why your doctor might prescribe metformin to treat PCOS, some of which are fertility-related.

Insulin Resistance

Insulin resistance is common in people with PCOS. Metformin can be prescribed to treat insulin resistance, which might help regulate reproductive hormones and restart ovulation.

Ovulation Induction

Some research on metformin and PCOS has shown that menstrual cycles become more regular and ovulation returns with treatment. In some cases, the effect occurs without needing fertility drugs like Clomid. However, some larger research studies did not find taking metformin to be beneficial.

Some doctors recommend that metformin only be used to treat people who are insulin-resistant—not all people with PCOS regardless of whether or not they are insulin-resistant.

Clomid Resistance

While Clomid will help some people with PCOS ovulate, there are also people who are Clomid-resistant (which means the drug does not work for them).

Some studies have indicated that taking metformin for 4 to 6 months before starting treatment with Clomid might improve success for some people who are resistant to Clomid. Another possible option is metformin combined with letrozole

Injectable Fertility Drugs

If Clomid doesn’t help you get pregnant, the next step is usually gonadotropins or injectable fertility drugs. Some research has found that combining injectables with metformin may improve ongoing pregnancy rates.

One study found that combining metformin with injectables improved the live birth rate when compared to treatment with injectables alone. In this study, if the live birth rate with injectables alone was 27%, while treatment with metformin and injectables boosted the live birth rate to between 32 to 60%. 

Reduced Risk for Ovarian Hyperstimulation Syndrome

Ovarian hyperstimulation syndrome (OHSS) is a possible risk when using fertility drugs, especially during IVF treatment. People with PCOS have a greater risk of developing OHSS.

Some studies have indicated that metformin might reduce the risk of OHSS during IVF. However, it’s unclear whether OHSS is reduced for other treatments. For example, research on gonadotropins alone (without IVF) did not find any difference in OHSS rates when adding metformin to the treatment protocol.

Repeated Miscarriage

People with PCOS might be more likely to experience miscarriage compared to the general population. A few studies have claimed that metformin might reduce the risk of miscarriage in patients with PCOS. However, many more studies did not find miscarriage reduction from metformin use.

For people who took metformin when trying to get pregnant, there has been some concern that stopping the drug once the pregnancy is confirmed might increase the risk of miscarriage.

However, studies have found that stopping metformin use does not increase the risk of miscarriage. Additionally, continuing to take metformin during the first trimester of pregnancy does not appear to reduce the miscarriage rate.

The safety of taking metformin during pregnancy is not well-documented. Your doctor might want you to stop taking it as soon as a fetal heartbeat is detected.

For Weight Loss

PCOS is linked to obesity. Maintaining a healthy weight or losing weight if you have the condition can be difficult. Some studies have shown that metformin might help some people with PCOS lose weight. 

Losing weight has been demonstrated to help restart ovulation and achieve pregnancy. Your doctor might prescribe metformin, along with a diet plan and exercise routine, to help you improve your fertility.

Metformin as a Fertility Drug

There are many reasons metformin might be prescribed to a person with PCOS when they are trying to conceive. However, this does not mean the medication can be used as a fertility drug.

During the early days of metformin use for PCOS treatment, doctors did prescribe the diabetes drug in hopes of inducing ovulation. Research has found that when metformin is compared to a placebo, the rate of ovulation increased.

The hope was that ovulation would lead to conception—which made metformin look like a possible option for fertility treatment. However, further research proved to be less hopeful.

While metformin alone might increase the odds of ovulation in some people, studies have not found that it increases pregnancy rates or live birth rates.

The boost in ovulation metformin can provide won't necessarily result in pregnancy success. Treatment with Clomid, Letrozole, or one of these drugs in combination with metformin, is a better option for fertility.

There are also over-the-counter supplements that claim to boost fertility because they contain substances that are natural insulin regulators. One example is myoinositol, a complex B-vitamin found in cantaloupe, brown rice, and sesame seeds. When taken in supplement form, it does not typically cause the gastrointestinal side effects that are common with metformin.

Ask your doctor before starting any supplement. While you might be able to get them OTC without a prescription, they can still interact with medications you are taking.

Side Effects of Metformin

Metformin's most common side effect is stomach upset, usually diarrhea. Vomiting and nausea can also occur. Taking metformin in the middle of a meal might help lessen these side effects.

Digestion-related side effects of metformin may lessen over time. Some people find that particular foods trigger more stomach upset than others.

More serious side effects associated with metformin are liver dysfunction and a rare but severe side effect called lactic acidosis.

While taking metformin, your doctor should monitor your kidney and liver functions. People with heart, liver, kidney, or lung disease should not take metformin. Be sure to provide your doctor with a thorough medical history.

A Word From Verywell

Doctors have opposing views on if, when, and how metformin should be used to treat infertility. The use of metformin as part of fertility treatment for people with PCOS is still being researched. If you have PCOS, you can discuss the risks and possible benefits of taking metformin with your doctor.

11 Sources
Verywell Family uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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By Rachel Gurevich, RN
Rachel Gurevich is a fertility advocate, author, and recipient of The Hope Award for Achievement, from Resolve: The National Infertility Association. She is a professional member of the Association of Health Care Journalists and has been writing about women’s health since 2001. Rachel uses her own experiences with infertility to write compassionate, practical, and supportive articles.