How Metformin Is Used for Fertility

What Is Metformin, Possible Side Effects, and Why It's Used for Infertility

Metformin is an insulin-sensitizing drug primarily used to treat diabetes, but it can also be used for fertility. Exactly how metformin improves fertility is unclear. 

Women with polycystic ovarian syndrome (PCOS) might benefit from taking metformin alone, with Clomid, or during IVF treatment.

While metformin can be used for the treatment of infertility, it is not a fertility drug. When taken to treat infertility, it is considered an off-label use (which means that pregnancy achievement is not the original intended purpose of the drug).

Here's an overview of what metformin is and how it might help you conceive.

How Metformin Works

To understand what metformin does, you first need to understand insulin resistance, as many women 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).

There seems to be a connection between insulin and reproductive hormones. It's not clear exactly how the two are connected, but insulin levels seem to lead to increased levels of androgens.

While both men and women have androgens, they are typically thought of as "male hormones." If women have high androgen levels it 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 Use 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 women with PCOS. Metformin can be prescribed to treat insulin resistance, which might help regulate the 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 women who are insulin-resistant—not all women with PCOS regardless of whether or not they are insulin-resistant.

Clomid Resistance

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

Some research studies have found that taking metformin for 4 to 6 months before starting treatment with Clomid might improve success for women who are Clomid-resistant. Another option for some women with Clomid resistance 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%, 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. Women 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

Women 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 women with PCOS. However, many more studies did not find miscarriage reduction from metformin use.

For women 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. Continuing to take metformin during the first trimester of pregnancy does not appear to reduce the miscarriage rate.

The safety of metformin during pregnancy is not well-documented. Given the lack of evidence that it is beneficial during pregnancy, you should discuss the risks of continuing the medication with your doctor.

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 women 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 woman with PCOS while she's 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 women, 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.

Side Effects

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 women 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 women with PCOS is still being researched. If you have PCOS, you can discuss the risks and possible benefits of taking metformin with your doctor.

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