How Metformin Is Used for Fertility

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

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Metformin is an insulin-sensitizing drug primarily used to treat diabetes, but it can also be used for fertility. Women with PCOS may benefit from taking metformin alone, along with Clomid, or even during IVF treatment. Exactly how metformin improves fertility is unclear.  

While metformin may be used for the treatment of infertility, it is not a fertility drug. In fact, using it to treat infertility is considered an off-label use.

(In other words, pregnancy achievement is not the original intended purpose of this drug.)

What is this medication? And how might it help you conceive?

What Is Metformin?

To understand what metformin does, you first need to know what insulin resistance is. Many women with PCOS have insulin resistance. Insulin resistance is when the body's cells stop reacting to normal levels of insulin. They become less sensitive, or resistant.

As a result, the body thinks that there is not enough insulin in the system. This triggers the production of more insulin than your body needs.

There seems to be a connection between insulin and the reproductive hormones. While no one is quite sure exactly how the two connect, insulin levels seem to lead to increased levels of androgens.

Men and women have androgens, but androgens are typically thought of as "male hormones." High androgen levels lead to PCOS symptoms and problems with ovulation.

Metformin and other insulin-sensitizing medications lower excess levels of insulin in the body. Besides metformin, rosiglitazone and pioglitazone are other insulin-sensitizing drugs that may be used to treat PCOS.

Why Is Metformin Used to Treat PCOS?

There are several reasons why your doctor may prescribe metformin when treating your PCOS, some of them fertility related:

Insulin Resistance

As stated above, insulin resistance is common in women with PCOS.

Metformin may be prescribed to treat insulin resistance, which may then help regulate the reproductive hormones and restart ovulation.

Ovulation Induction

Some research on metformin and PCOS shows that menstrual cycles become more regular and ovulation returns with the treatment of metformin. This may happen without needing fertility drugs like Clomid.

However, some larger research studies did not find a benefit to taking metformin.

For this reason, some doctors are recommending that metformin be used only to treat women who are insulin-resistant and not all women with PCOS regardless of whether or not they are insulin-resistant.

Clomid Resistance

While Clomid will help many women with PCOS ovulate, some women are Clomid-resistant. (This is a fancy way of saying that it doesn't work for them.)

Some research studies have found that taking metformin for 4 to 6 months before starting Clomid treatment may improve success for women who are Clomid-resistant.

Another option for women with Clomid resistance may be 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.

Research has found that combination injectables with metformin may improve ongoing pregnant 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 percent, treatment with metformin and injectables would boost the live birth rate up to 32 to 60 percent. 

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 an even greater risk of developing OHSS.

Some studies have found that metformin may 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 may be more likely to experience miscarriage than the general population. Metformin may reduce the risk of miscarriage in women with PCOS, according to some studies.

A few studies have found that continued metformin treatment during the first trimester of pregnancy may also help prevent miscarriage in women with PCOS.

However, the safety of metformin during pregnancy is not well-documented. Deciding to take metformin during pregnancy is a risk that should be carefully discussed with your doctor.

For Weight Loss

PCOS is linked to obesity. To the frustration of many women, losing weight with PCOS may be more difficult.

Some studies have shown that metformin can help women with PCOS lose weight. Since losing weight has been demonstrated to help restart ovulation and achieve pregnancy, your doctor may prescribe metformin, along with a diet plan and exercise routine, to help improve your fertility.

What Are the Side Effects?

Metformin's most common side effect is stomach upset, usually diarrhea, but sometimes also vomiting and nausea. Taking metformin in the middle of a meal may help lessen this side effect.

Digestion related side effects 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, 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.

The use of metformin to treat infertility related to PCOS is still being researched, and different doctors have opposing views on if, when, and how to use metformin to treat infertility. 

Don't be afraid to voice your concerns and questions to your care provider, so that together, you can decide if this treatment is for you.

Sources:

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Nawaz FH, Rizvi J. "Continuation of metformin reduces early pregnancy loss in obese Pakistani women with polycystic ovarian syndrome." Gynecologic and Obstetric Investigation. 2010; 69(3):184-9. Epub 2009 Dec 21.

Roy KK, Baruah J, Sharma A, Sharma JB, Kumar S, Kachava G, Karmakar D. "A prospective randomized trial comparing the clinical and endocrinological outcome with rosiglitazone versus laparoscopic ovarian drilling in patients with polycystic ovarian disease resistant to ovulation induction with clomiphene citrate." Archives of Gynecology and Obstetrics. 2010 May; 281(5):939-44. Epub 2009 Dec 3.

Tso LO1, Costello MF, Albuquerque LE, Andriolo RB, Macedo CR. “Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome.” Cochrane Database Syst Rev. 2014 Nov 18;(11):CD006105. doi: 10.1002/14651858.CD006105.pub3.

Yu Y1, Fang L1, Zhang R1, He J1, Xiong Y1, Guo X1, Du Q1, Huang Y1, Sun Y2. “Comparative effectiveness of 9 ovulation-induction therapies in patients with clomiphene citrate-resistant polycystic ovary syndrome: a network meta-analysis.” Sci Rep. 2017 Jun 19;7(1):3812. doi: 10.1038/s41598-017-03803-9.

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