What Are Fertility Pills?

If you’re having trouble becoming pregnant, you may have heard about fertility pills. Clomiphene (Clomid) and letrozole (Femara) are the most common examples. These medications can help people who have trouble ovulating, a key step in becoming pregnant.

In this article, we’ll break down how fertility pills work, their differences, and what to expect when taking them.

How do fertility pills work?

During a typical menstrual cycle, your ovaries develop and release one mature egg. This timed process is controlled by the following hormones:

• Follicle-stimulating hormone (FSH) stimulates the follicles in your ovaries to grow and develop into a mature egg.

• Estrogen is released by follicles as they mature. Typically, one main follicle takes over to become a single mature egg. High estrogen levels signal to the brain that a mature egg is present.

• Luteinizing hormone (LH) is released in response to high estrogen levels. This signals the ovary to release the mature egg into the fallopian tube, so it can become fertilized.

Clomiphene and letrozole help with ovulation by changing the levels of these hormones. But they work in slightly different ways.

Clomiphene

Clomiphene is a selective estrogen receptor modulator (SERM). It works by blocking estrogen from binding to estrogen receptors (chemical binding sites) in the brain and ovaries. This tricks the body into thinking estrogen levels are low. Low estrogen tells the body that follicles aren’t developing. In response, your body will release more FSH. This helps increase the chance that a mature egg will develop.

Letrozole

Letrozole also increases FSH levels. But it does this in a different way from clomiphene. Letrozole is an aromatase inhibitor. Aromatase is an enzyme (protein) that helps turn androgens (such as testosterone) into estrogen in the body. Blocking aromatase lowers estrogen levels, which triggers the brain to release more FSH.

Blocking aromatase also increases the levels of androgens in the ovaries. This can make follicles more sensitive to FSH, which also increases the chance that a mature egg will develop.

When are fertility pills prescribed?

Fertility pills are typically prescribed when there’s a possible issue with ovulation. They’re often used as part of infertility treatments, such as timed intercourse or intrauterine insemination (IUI). They’re sometimes used as part of in vitro fertilization (IVF), but that’s not as common.

These medications are also first-choice treatments for infertility associated with polycystic ovary syndrome (PCOS). That’s because PCOS often causes problems with ovulation.

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In most cases, you’ll need to try to get pregnant on your own for at least 1 year before trying fertility pills. Your healthcare team can help you determine if and when they’re an option for you based on your personal history.

What’s the difference between clomiphene and letrozole?

As mentioned, clomiphene and letrozole both increase FSH levels to help stimulate ovulation. But there are some key differences to consider between these fertility pills.

FDA approval

Only clomiphene is FDA approved for infertility. Letrozole is approved only as a breast cancer treatment. So it’s prescribed off-label for infertility. But studies suggest that it’s just as effective as clomiphene — more on that later.

Side effects

Clomiphene and letrozole also have different side effects to consider.

Common letrozole side effects include fatigue, nausea, and hot flashes. Dizziness is also possible. Keep in mind that these side effects were reported in clinical studies on letrozole as a breast cancer treatment. When letrozole is taken for infertility, it seems that muscle and joint pain and mild headache are more likely.

Common clomiphene side effects include hot flashes, bloating, and sore breasts. Hot flashes seem to be more common with clomiphene than with letrozole. Clomiphene can also cause your ovaries to become swollen and can make you feel bloated.

In rare cases, too many follicles can develop at once. This may lead to a serious side effect known as ovarian hyperstimulation syndrome (OHSS). OHSS is more common with injected fertility medications, but it can happen with clomiphene in rare cases. Letrozole, on the other hand, is sometimes used to help prevent OHSS from happening.

Clomiphene may also have side effects that affect fertility. It can reduce the quality of cervical mucus and the development of the endometrium (lining of the uterus). Both of these side effects can make it harder to become pregnant, even if ovulation occurs. But letrozole doesn’t seem to cause these side effects.

How effective are fertility pills?

Clomiphene and letrozole are both considered effective first-choice infertility treatments.

Studies show that ovulation occurs in about 75% to 80% of people taking clomiphene. But not everyone responds to treatment. It’s estimated that anywhere from 15% to 40% of people won’t ovulate after taking clomiphene. If you don’t ovulate after three cycles of clomiphene, your fertility care team will likely consider a different treatment option.

Letrozole and clomiphene are considered similarly effective, except in people living with PCOS. Several clinical reviews show that letrozole treatment has a higher rate of ovulation, pregnancy, and live births than clomiphene in people with PCOS.

The effectiveness of fertility pills also depends on other factors. You can help increase the chance of pregnancy by making lifestyle changes, such as:

• Avoid smoking.

• Limit alcohol and caffeine.

• Maintain a healthy body weight.

• Eat a nutritious diet.

Do fertility pills increase your chances of having multiples?

Yes, fertility pills can increase the chance of a multiple pregnancy, such as having twins or triplets. This can happen if more than one follicle develops and releases an egg.

Letrozole seems less likely than clomiphene to lead to a multiple pregnancy. But study results are mixed, and some show a similar rate of multiples with either medication.

How long do you have to take fertility pills?

In most cases, you’ll take clomiphene or letrozole for 5 days during your menstrual cycle.

You’ll typically start taking clomiphene around day 5 of your cycle (day 1 is the first day of your period). Letrozole treatment usually starts on day 3. For both medications, ovulation should occur about 5 to 10 days after starting treatment.

If you don’t ovulate after the first cycle of fertility pills, your prescriber may increase your dose. If you don’t ovulate or become pregnant after three treatment cycles, a different fertility medication may be a better option for you.

Are there other fertility pills available?

There are other oral medications that help support specific causes of infertility:

• Metformin (Glucophage), a medication that treats Type 2 diabetes, can also help improve fertility. It’s typically prescribed for people living with PCOS to help support ovulation.

• Bromocriptine (Parlodel) and cabergoline are used in people with high prolactin levels (hyperprolactinemia). Prolactin is a hormone that helps balance estrogen and testosterone in the body. If your prolactin level goes too high, it can prevent ovulation from happening. These medications reduce prolactin levels to increase the chance of ovulation.

Many other types of medication are used to help support fertility. Often, these medications are injected or inserted vaginally instead of taking them by mouth. Your fertility team can discuss the options available to you.

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Written by:

Stacia Woodcock, PharmD

Stacia Woodcock, PharmD, is a pharmacy editor for GoodRx. She earned her Doctor of Pharmacy degree from the University of Kentucky and is licensed in New York and Massachusetts.

Reviewed by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

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