Letrozole for Fertility: Success Rates, Side Effects, and What to Expect

When patients come to see me, many of them are feeling frustrated and defeated, especially when it comes to the challenge of ovulation. If you’re not ovulating regularly—or at all—then getting pregnant can feel like an impossible task. That’s when medications like letrozole, also known by the brand name Femara, come into play, offering a lifeline to women struggling with fertility.

My name is Dr. Lucky Sekhon and I am a practicing reproductive endocrinologist (REI) and author of this blog. I help hundreds of women each year in helping to overcome infertility with treatments such as IVF and IUI, which often involve the use of a ovulation induction drug such as letrozole. If you’ve been researching fertility treatments, you may have already heard of letrozole. It’s been a game-changer in my practice, especially for women with conditions like PCOS (polycystic ovary syndrome). In this post, I’ll walk you through how letrozole works, who it’s right for, and what you can expect from the process.

I have previously done a similar break down on the other commonly used ovulation induction drug Clomid, which you can find here.

Note to the Reader: As you read this post, you may wonder why I am not capitalizing ‘letrozole’, while on the other hand I do capitalize ‘Clomid’? The reason is that typically in medicine we only capitalize the branded version of a drug (ie. Clomid or Femara), while the generic name referencing the unbranded drug is not (ie. Letrozole).

What is Letrozole?

Letrozole wasn’t originally designed for fertility—it’s actually a medication that was developed to treat breast cancer. But in the world of reproductive medicine, we’ve found that it has an amazing “off-label” use for helping women ovulate.

By blocking estrogen production, letrozole sends a signal to your brain that estrogen levels are low, prompting your body to release more follicle-stimulating hormone (FSH). This increase in FSH stimulates your ovaries to mature an egg and, hopefully, trigger ovulation. For my patients who struggle with ovulatory dysfunction, like those with PCOS, letrozole can make the difference between months of disappointment and that long-awaited positive pregnancy test.

How Does Letrozole Work for Ovulation Induction?

Let me break down the science a bit. Letrozole works by reducing estrogen levels, which tricks your brain into thinking there isn’t enough estrogen. This prompts the release of more FSH, which helps your ovaries develop and release a mature egg.

I think about Sarah, a patient of mine with PCOS. She had been on Clomid for several cycles without success. Every time we monitored her, we saw poor follicle growth and an overly thin uterine lining—both side effects of Clomid that were working against her chances of pregnancy. When we switched her to letrozole, her body responded beautifully. Her follicles grew to the right size, and her uterine lining thickened just enough for implantation. Two cycles later, Sarah saw those two pink lines.

Letrozole, unlike Clomid, doesn’t interfere with the uterine lining or cervical mucus, which can make all the difference when you’re trying to conceive. That’s why it’s becoming a preferred option in many cases.

Who Is Letrozole Recommended For?

In my practice, I’ve seen letrozole work best for women with PCOS, who often struggle with irregular or absent ovulation. It’s also great for women with unexplained infertility or those who haven’t responded well to Clomid. I’ve had many patients who came to me after months of trying Clomid with no success. When we made the switch to letrozole, many of them had success after just a couple of cycles.

Take another one of my patients, Jessica. She didn’t have PCOS, but she and her partner had been trying to conceive for two years with no clear reason for why it wasn’t happening. After a few failed rounds with Clomid, we started her on letrozole, and she responded well. After four cycles of ovulation induction and timed intercourse, she was able to get pregnant.

Letrozole vs. Clomid: Which Is Better for Fertility?

Both letrozole and Clomid have their place in fertility treatment, I previously have written a post comparing Clomid to letrozole, which you can find here. Generally, I often recommend letrozole for women with PCOS. Research, and my own experience with patients, shows that letrozole can lead to better ovulation and pregnancy rates for these women. However, as always, I am speaking in generalities here and you should speak to your REI about which drug is right for you.

In the famous PPCOS II study, women with PCOS had higher live birth rates on letrozole compared to Clomid. What I’ve found in practice mirrors this research. Patients with PCOS are often more responsive to letrozole, and I see less thinning of the uterine lining—a common issue with Clomid.

Here’s a quick comparison of both drugs:

Feature	Letrozole	Clomid
Ovulation rates	Higher in women with PCOS	Lower for PCOS
Uterine lining effects	No thinning	May thin the lining
Risk of multiple pregnancy	Lower (2-3%)	Higher (5-10%)
Side effects	Mild (headaches, fatigue)	More severe (mood swings, hot flashes)

What Is the Letrozole Treatment Process Like?

Letrozole treatment is relatively straightforward, but there are a few steps that we walk through in the clinic to maximize your chances of success:

1. Starting the Medication: I usually have patients start letrozole on day 3-5 of their menstrual cycle.
2. Monitoring Follicle Growth: We’ll use ultrasounds to track how your follicles are developing. This typically happens around day 10-14 of your cycle.
3. Ovulation Timing: Once we see a mature follicle, we may trigger ovulation with an hCG shot. From there, we time intercourse or schedule intrauterine insemination (IUI) based on your cycle.
4. Tailored Dosages: Depending on how your body responds, we might adjust the dosage for future cycles. Some women ovulate on a lower dose, while others need a bit more stimulation.

I recently worked with a patient named Mia, who was having trouble ovulating regularly. Her initial response to letrozole was a bit slow, so we increased her dose slightly in her second cycle, and that made all the difference. After tracking her ovulation with ultrasounds and perfectly timing her IUI, she finally achieved the pregnancy she had been dreaming of through IUI.

What Are the Success Rates of Letrozole for Fertility?

The success rates of letrozole are promising, especially for women with PCOS. A study done in 2020 has shown that up to 93% of women with PCOS will ovulate on letrozole, versus about 83% on Clomid.

Success depends on several factors, like your age, ovarian reserve, and the underlying cause of your infertility. But in my own practice, I’ve seen letrozole make a huge impact, especially for patients who didn’t ovulate with Clomid or had unexplained infertility.

Side Effects and Risks of Letrozole

Letrozole tends to be well-tolerated, but like any medication, there are some potential side effects. The most common ones include headaches, fatigue, and occasional hot flashes. From my experience, most women find the side effects manageable, and they’re typically milder than those associated with Clomid.

One of the biggest benefits of letrozole over Clomid is that it has a lower risk of multiple pregnancies. The chance of twins or more is about 2-3% with letrozole, which is much lower than the 5-10% chance with Clomid.

Who Should Avoid Letrozole?

Letrozole isn’t for everyone. If you’re already pregnant, letrozole is not safe to take. It should also be avoided if you’re breastfeeding or have certain medical conditions that could make the drug unsafe for you. Your fertility specialist will review your health history to make sure letrozole is the right option.

FAQs About Letrozole for Fertility

Here are some common questions I get from my patients when discussing letrozole:

Can I use letrozole if I don’t have PCOS?

Yes! Letrozole can be used for women with unexplained infertility or those who haven’t responded to other medications like Clomid.

How many cycles of letrozole should I try before moving on to other treatments?

I typically recommend trying letrozole for 3-6 cycles. If it doesn’t work after that, we may explore injectable medications or in vitro fertilization (IVF). However, this really depends on your own body and medical context, please do not take this as medical advice, you and your doctor need to discuss what treatment plan is best for you.

What happens if letrozole doesn’t work?

If letrozole doesn’t lead to ovulation or pregnancy after several cycles, we’ll explore other options. Some patients respond better to injectable fertility medications or may need to consider IVF.

Conclusion

While letrozole has proven to be a highly effective option for many women, particularly those with PCOS, it’s important to remember that every fertility journey is unique. What works well for one person may not be the right fit for another. The decision about which medication to use—whether it’s letrozole, Clomid, or another treatment—should always be made in partnership with your fertility specialist.

There are many factors to consider, such as your age, overall health, specific fertility diagnosis, and how your body responds to different medications. These general guidelines can help you better understand what letrozole can offer, but the best next step is having a personalized conversation with your REI (Reproductive Endocrinologist and Infertility Specialist) to discuss your unique situation and goals.

Ultimately, your fertility treatment plan should be customized to you, and I encourage you to work closely with your doctor to find the approach that gives you the best chance for success.

As I mentioned earlier in the post, my name is Dr. Lucky Sekhon, and I am a fertility specialist here in New York City. I regularly produce content on this blog and my Instagram relating to fertility, and women’s reproductive health. If you want to stay up to date on the latest content I produce, I encourage you to sign up for my monthly newsletter, the Lucky Egg Drop. If you are suffering from infertility and are interested in booking a consultation with me at my New York office, please submit an appointment request here.