Is Letrozole effective as a fertility treatment?

Letrozole is currently gaining ground as a fertility treatment. It's currently not FDA-approved for fertility, but there's solid evidence that letrozole for fertility can be effective for some women, particularly those with PCOS-related infertility. 

What is Letrozole?

Letrozole is a medication given in pill form as an aromatase inhibitor. Aromatase inhibitors work by blocking aromatase, which converts androgens like testosterone into estrogen. Letrozole is FDA-approved to treat estrogen-sensitive breast cancer in postmenopausal women, because it reduces the amount of estrogen in the body.

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Letrozole for Ovulation

Letrozole for infertility is effective for infertility because it can induce ovulation. Lack of ovulation is the cause of infertility in about 25% of women with fertility problems. It's a good option for infertility due to PCOS because PCOS impacts hormones, making ovulation unpredictable or preventing it completely. Either of these issues makes it difficult to conceive. 

How Letrozole Works for Infertility 

Premenopausal women who take Letrozole will have reduced estrogen levels. This leads to other hormones, particularly follicle stimulating hormone or FSH, increasing. The increase in FSH can cause a follicle in the ovary to mature, which leads to ovulation. This process is called "induction of ovulation". Once ovulation occurs, there's an opportunity to conceive if the egg is fertilized. 

Superovulation 

Superovulation occurs when multiple eggs are released at one time. This typically occurs when a woman who can ovulate without Letrozole takes the medication.  The release of multiple eggs increases the chances of pregnancy compared to the release of a single egg. 

This means that letrozole can improve the odds of pregnancy for women struggling to conceive, even if they ovulate regularly. 

Letrozole for Fertility Success Rate

The success rate for Letrozole will depend on several factors, including the female's age and reproductive health. 

Letrozole for PCOS Infertility Success Rate 

Studies have shown that letrozole can be highly effective for fertility, particularly for PCOS-induced infertility. In women who didn't ovulate due to PCOS, 70% ovulated when taking Letrozole. 

Pregnancy rates for women with PCOS are 20-27% with Letrozole, with chances increasing based on the number of cycles. After 5 cycles, the chances of a live birth are 27% to 28% with Letrozole. 

Letrozole for Non-PCOS Induced Infertility 

While data for non-PCOS-induced infertility is limited, Letrozole should still be considered. 

Letrozole can be a good option for unexplained infertility. Unexplained infertility occurs when a woman can't conceive, but there's no identifiable medical issue preventing conception. Letrozole is as effective as other medications, like Clomid, and can be a reasonable alternative. 

For women who are unable to ovulate due to a cause other than PCOS, Letrozole can be effective, particularly if Clomid has failed. 

Letrozole can also be helpful for infertility associated with mild endometriosis. It's believed to be as effective as Clomid in this case. 

Lastly, Clomid can thin the uterine lining, which makes implantation more difficult. Letrozole has less impact on the uterine lining, so it can improve fertility if uterine thinning is an issue. 

Side Effects of Letrozole for Fertility

Like any medication, Letrozole can cause side effects. Some side effects are similar to those experienced during menopause, because Letrozole lowers estrogen levels. While rare, some side effects of Letrozole can be severe. 

Common Side Effects of Letrozole

Common side effects of Letrozole occur in more than 1 in 100 people. These side effects typically resolve within a few months of starting treatment. However, if your symptoms are severe or last longer than a few months, contact your doctor. 

Common side effects of Letrozole include:

• Hot flushes and sweating
• Bleeding from your vagina
• Fatigue
• Nausea or vomiting
• Loss of appetite
• Aches in muscles or bones
• Hair loss
• Depression 
• Insomnia 

Serious Side Effects of Letrazole

Serious side effects of Letrazole are rare, which means they happen in less than 1 in 100 people. If you experience these side effects, contact your healthcare provider. 

Serious side effects include:

• Swelling, warmth, or throbbing in an arm or leg, which can indicate a blood clot
• Pain, swelling, or weakness in your joints or tendons 
• Fever or chills, which can indicate an infection
• Frequent mouth ulcers or sore throat
• Yellow skin tone or yellow in the whites of your eyes can indicate liver problems
• Frequent or painful urination, which can indicate a UTI
• Blurred vision
• Difficulty breathing, swelling of the face or throat, hives, and dizziness can indicate an allergic reaction

Potential Long-Term Effects

Potential long-term effects include osteoporosis, increased blood pressure, and higher cholesterol levels. Your doctor may monitor your bone density while you are taking Letrozole. 

Multiple Pregnancies 

Because Letrozole can cause more than one egg to be released in a cycle, it also increases the risk of multiples. Carrying twins, triplets, or more increases the risks of complications. However, Letrozole has a lower risk of multiples than Clomid. 

Ovarian Hyperstimulation Syndrome (OHSS)

Ovarian Hyperstimulation Syndrome, or OHSS, is a rare but serious side effect of Letrozole. This occurs when the ovaries are overly stimulated by fertility treatments. The condition can range from mild to severe. Mild cases cause bloating and slight weight gain. Severe cases are rare, but can be life-threatening. While Letrozole can cause OHSS, it's less likely to do so than Clomid. 

Foods to Avoid While Taking Letrozole for Fertility 

While there are no foods that are prohibited when taking Letrozole, there are some foods that you should consider avoiding. 

Grapefruit Juice

Grapefruit juice is processed by the CYP3A4 enzyme. Many medications, including Letrazole, are also processed by this enzyme. Drinking grapefruit juice, particularly around the same time you take Letrozole, can impact how the body breaks down the medication.

Alcohol 

Some people experience hot flashes and flushing when taking Letrozole and drinking alcohol. While there's no evidence of a serious interaction, if alcohol causes these symptoms, it's best to avoid it. 

Phytoestrogens 

It's been suggested that foods high in phytoestrogens, like soy, can mimic estrogen in the body. These foods could be counterproductive when taking Letrozole. Small amounts of soy in food are okay, but avoid excessive consumption of phytoestrogens or soy supplements. 

Carbohydrates 

Carbohydrates, particularly simple sugars and starches, can raise your blood sugar. If you have PCOS, you may already struggle with high blood sugar levels. If you struggle with fertility due to endometriosis, carbohydrates can exacerbate the inflammation associated with the condition.

Eating a balanced diet that's low in simple carbs like sugar, soda, candy, white bread, rice, and crackers can support your overall health and fertility. 

Saturated Fats

Letrozole can increase your cholesterol, so it's wise to limit your consumption of saturated fats when taking the medication. Saturated fats include butter, whole milk, red meat, cheese, and palm oil.  

Caffeinated Beverages 

While there are no known interactions between Letrozole and caffeine, some women experience insomnia as a side effect of the medication. If you have difficulty sleeping while taking Letrozole, caffeine can make the issue worse. Try to limit caffeinated drinks like tea, coffee, and sodas, particularly in the hours before bedtime. 

Using Letrozole for Fertility 

Generally, it's recommended to begin by taking 2.5 mg once daily for five days. You'll want to start the medication between days two and five of your menstrual period. You can take it at any time of day, but you should take it around the same time each day. 

Your doctor will typically monitor you to see when you are ovulating. Once you are ovulating, there are a few options to consider. 

Timed Sexual Intercourse 

Timed sexual intercourse means that you and your partner will have intercourse during your ovulation window. You may be encouraged to have intercourse several times during this window if possible. While this method is not the most effective, it is the simplest and most cost-effective. 

Intrauterine Insemination 

Intrauterine insemination involves inserting the sperm directly into the uterus. It's a simpler and less invasive procedure than in vitro fertilization, and typically less expensive as well. This method typically has a success rate higher than timed intercourse, but less than in vitro fertilization, although this can vary depending on the cause of infertility. 

In Vitro Fertilization 

In vitro fertilization, or IVF, is a more invasive procedure. The process begins by stimulating the ovaries to produce multiple eggs, which are then harvested. When the woman is ovulating, an egg or eggs will be fertilized in the lab, and then implanted into the uterus. IVF is a longer time commitment, requiring multiple appointments, but has a higher success rate. In women under 35, the success rate can be as high as 40%-50%. 

Continued Cycles 

If the first cycle doesn't result in pregnancy, the process can be repeated. Typically, the Letrozole dose is increased by 2.5 mg increments up to 7.5 mg. There's no set number of cycles, although around 5 is common. 

Final Thoughts on Letrozole for Infertility 

We've answered the question "What does Letrozole do for fertility?". Letrozole can be a helpful treatment, particularly for women who do not ovulate regularly. Letrozole is a suitable alternative to Clomid, and can offer success in cases where Clomid has failed. While the highest success rate is seen in women with PCOS-induced infertility, it can be helpful for other causes of infertility as well.  

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