If you and your partner are struggling to conceive, you may be exploring different options to help you get pregnant. Two of the most commonly prescribed fertility medications are Letrozole (often known by the brand name Femara) and Clomiphene Citrate (known as Clomid or Serophene).
This post provides a side-by-side comparison of Letrozole and Clomid, including their success rates, side effects, and associated costs.
What is Letrozole (Femara)?
Letrozole is an oral medication that was originally approved by the Food and Drug Administration (FDA) to treat certain types of breast cancer in postmenopausal women. However, fertility specialists frequently prescribe it “off-label” to help women with ovulatory dysfunction get pregnant. This means it’s used for a purpose other than what it was initially approved for, which is a common and safe practice in medicine when research supports its effectiveness.
How Letrozole Works
Letrozole belongs to a class of medications known as “aromatase inhibitors.” Aromatase is an enzyme in the body that’s responsible for converting hormones (androgens) into estrogen. Letrozole works by temporarily blocking this enzyme, which leads to a decrease in estrogen production.
When your brain detects these lower estrogen levels, it thinks your body needs to produce more. So, it sends signals to your pituitary gland to release more follicle-stimulating hormone (FSH) and luteinizing hormone (LH). These hormones help the ovarian follicles develop and release mature eggs.
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What is Clomid (Clomiphene Citrate)?
Clomiphene citrate, widely known as Clomid or Serophene, is an FDA-approved oral medication that’s been used for more than 50 years to treat infertility in women. It’s typically prescribed for women who don’t ovulate regularly or at all, which is common in conditions like polycystic ovary syndrome (PCOS).
How Clomid Works
Clomid is a selective estrogen receptor modulator. It works by tricking your brain into thinking that your estrogen levels are lower than they actually are. It does this by binding to estrogen receptors in the hypothalamus (a part of your brain).
This “trick” prompts the hypothalamus to release more gonadotropin-releasing hormone (GnRH), which then signals the pituitary gland to produce more FSH and LH. Just like with Letrozole, these increased levels of FSH and LH encourage your ovaries to develop and release an egg.
Letrozole vs Clomid: What are the differences?
Letrozole and Clomid are both effective fertility medications that can help women ovulate and get pregnant. However, the way that they do this, their side effects, and success rates can vary.
Ovulation Induction
For women with ovulatory disorders such as PCOS, research indicates that Letrozole may be somewhat more effective at inducing ovulation. This may be because Letrozole doesn’t have the same anti-estrogenic effects on the uterine lining as Clomid. Thin uterine lining can sometimes negatively interfere with implantation. However, it’s worth noting that some studies have found similar ovulation rates between the two.
If Clomid hasn’t worked for you in the past (sometimes called “Clomid resistance”), Letrozole can be a successful alternative.
Live Birth Rates
When it comes to live birth rates, especially for women with PCOS, studies have shown that Letrozole may lead to a higher chance of a live birth compared to Clomid. For women with unexplained infertility, the results are mixed showing similar success rates for both medications.
Your fertility specialist can assess your specific situation and help you decide which medication is most likely to lead to a successful pregnancy.
Side effects
Both medications can have side effects, and it’s helpful to know what to expect.
With Letrozole, you might experience fatigue, dizziness, headaches, hot flashes, or joint and muscle pain.
Clomid can cause hot flashes, bloating, headaches, or breast tenderness. It’s also important to be aware of less common but more serious side effects, like changes in vision. A notable difference with Clomid is that it can sometimes cause a thinner uterine lining (endometrium), which might make it harder for an embryo to implant. It can also cause your cervical mucus to become thicker, potentially making it more challenging for sperm to reach the egg.
It’s also worth noting that both Letrozole and Clomid can increase your chance of having a multiple pregnancy, like twins or triplets, since they work by stimulating your ovaries to release more than one egg but the chances are overall low.
Generally, Letrozole is associated with fewer overall side effects than Clomid. As always, it’s a good idea to speak with your doctor to understand the potential side effects of each medication and what they might mean for you.
Cost
Both Clomid and Letrozole are relatively affordable oral medications, especially in their generic forms. The exact cost can vary depending on your pharmacy, insurance coverage, and location.
The good news is that both are often covered by insurance at similar rates, but even if they’re not, there are ways to potentially save money, including:
- Download GoodRx: If you’re paying out-of-pocket, websites like GoodRx can help you compare prices at different pharmacies in your area and find coupons that can reduce the cash price.
- Check with your pharmacy: Ask your local pharmacy about their cash price or if they have any in-store discounts or loyalty programs. Prices can vary from one pharmacy to another.
- Manufacturer savings programs: Some pharmaceutical companies offer patient assistance programs or savings cards for their fertility medications. Your fertility clinic or pharmacist might be aware of these programs and can help you determine if you qualify.
- Patient assistance programs and grants: Various non-profit organizations offer financial assistance or grants for fertility treatments, including medications.
Case Study: Switching from Clomid to Letrozole Improved Pregnancy Outcomes
Background
This case study is based on real patient experiences, with details modified to protect privacy. A 32-year-old woman with polycystic ovary syndrome (PCOS) had been trying to conceive for nearly two years while working with her OB/GYN. Her OB/GYN initially prescribed Clomid to stimulate ovulation. Although she ovulated on the medication, after six cycles she had not achieved pregnancy.
Approach
After visiting an RMA fertility clinic and discussing all available options, her fertility specialist recommended switching to Letrozole. The treatment plan included:
- Medication change: Discontinued Clomid and began Letrozole at a standard dose.
- Monitoring: Ultrasound monitoring was used to track follicle development and confirm ovulation.
- Timing support: The care team provided guidance on timing intercourse around the fertile window.
Results
The switch to Letrozole produced several notable differences:
- Ovulation Quality: Ultrasound monitoring showed thicker endometrial lining (8.5 mm vs. 6 mm on Clomid).
- Side Effects: The patient reported fewer side effects — less bloating and no changes in vision, compared to Clomid cycles.
- Pregnancy Outcome: On her third Letrozole cycle, she achieved a successful pregnancy.
Outcome
This case illustrates why Letrozole is often recommended for women with PCOS. In her situation, Letrozole improved endometrial lining, reduced side effects, and ultimately led to conception after Clomid had not.
Takeaway
While every patient is different, clinical research and real-world experience both suggest that Letrozole may offer better pregnancy outcomes for women with PCOS compared to Clomid. The key is working closely with a fertility specialist to find the right treatment approach and to use monitoring for safe and effective results.
Conclusion
Both Letrozole and Clomid are valuable and effective oral medications for stimulating ovulation and helping people achieve pregnancy. They are often a first-line treatment due to their effectiveness and lower cost compared to more advanced infertility treatment options, like injectable medications, intrauterine insemination (IUI), and in vitro fertilization (IVF). They are also frequently used in combination with IUI.
For many women, particularly those with PCOS, current research suggests that Letrozole may offer slightly better live birth rates and a more favorable side effect profile, especially concerning the uterine lining and the chance of multiple pregnancies (Letrozole tends to result in fewer multiple pregnancies compared to Clomid).
FAQ
What are the odds of twins on Letrozole vs Clomid?
Both medications can increase the chance of conceiving twins or other multiples, but the risk is generally lower with Letrozole. This is because Letrozole tends to encourage the development of a single dominant follicle (egg), while Clomid can sometimes lead to more follicles maturing at once. The risk of multiple births with Clomid is approximately 8-10%, while with Letrozole, it’s typically lower, often around 3-5%.
How long does it take to get pregnant on Letrozole?
Ovulation usually occurs five to 10 days after your last dose of Letrozole. Your doctor will guide you on timing intercourse around this “fertile window” based on ultrasound and blood work results. They may also order a blood test to check your progesterone levels about a week after expected ovulation to confirm ovulation. After your fertile window, your doctor will advise you on when to take a pregnancy test to see if the treatment was successful.
Does Letrozole make you ovulate more eggs?
Letrozole’s primary goal is to help you ovulate at least one healthy egg. While it can sometimes lead to the development of more than one egg, it’s generally more likely to result in a single dominant follicle compared to Clomid. This is one reason it’s often preferred for reducing the risk of multiple pregnancies.
Can I take Letrozole and Clomid together?
Typically, Letrozole and Clomid are not taken together. They work through similar pathways to stimulate ovulation, and combining them isn’t usually recommended or necessary. Your doctor will prescribe the medication they believe is most effective for your specific situation.
A Word from RMA
Navigating fertility treatment can feel overwhelming, but you don’t have to do it alone. If you’re considering oral medications like Letrozole or Clomid, or if you’ve been trying to conceive and are unsure of your next steps, speaking with a fertility specialist is a great idea.
The team at RMA Network has over 25 years of experience helping couples build their families. We’re here to answer your questions and guide you through the process. Contact us today to schedule a consultation.
