Written by Suzanne Zuppello and medically reviewed by Dr. Nateya Carrington of Radiance Women’s Center in Orlando, Florida.
When trying to get pregnant, your doctor will explore a number of potential causes for infertility. Depending on what they learn from your exam and medical history, the doctor might prescribe letrozole. Here is our guide to help you understand what this medication is and how it can help you conceive.
Letrozole For Fertility & Getting Pregnant
Letrozole is the generic name for the prescription drug Femara. Similar to Clomid, letrozole is used to stimulate ovulation in someone who wishes to become pregnant. Letrozole is typically prescribed by an ObGyn or fertility specialist but, depending on your circumstances, your primary care physician may write you a prescription. When prescribed letrozole, the dosing and dates on which it is taken are very precise and based on an individual’s unique cycle, which is why your doctor will want you to closely track your ovulation either in their office or using a simple at-home ovulation predictor kit.
What is Letrozole?
Letrozole was first approved by the Food and Drug Administration as an oral medication used in people with early stage breast cancer. The drug is an aromatase inhibitor — that means it prevents the conversion of androgen to estrogen, suppressing the production of estrogen in a person’s system. Given the effect it has on estrogen levels, fertility specialists began using it on patients with unexplained infertility or polycystic ovarian syndrome who did not respond to Clomid or couldn’t take it for other reasons.
How does Letrozole help with infertility issues?
Letrozole is most helpful in inducing ovulation in people who do not ovulate or to increase egg production in those who already do. It might seem strange to use a medication that suppresses estrogen while trying to get pregnant, but when timed properly, the medication supports your body’s natural process of ovulation. When estrogen levels drop, your body responds by producing the follicle stimulating hormone (FSH) to help maintain hormonal balance. However, the FSH also prompts the ovaries to grow more follicles and letrozole gives this process a boost, releasing more eggs and increasing one’s chance at natural conception or extracting eggs for freezing. It’s also believed that letrozole improves endometrial thickness, which is helpful for the implantation of an early pregnancy.
As mentioned, letrozole is taken at very precise times during your cycle. Some doctors believe taking it on days three through seven of your cycle, while others recommend using letrozole on days five through nine. Letrozole can be used with regular intercourse, ICI, or IUI. Typically, you’ll want to begin having sex (or inseminating) before you ovulate and continue every day from days 11 to 18, if you start on day three, and days 13 to 21, if you start on day five. Ovulation predictor tests can help you narrow this window by using them after you finish your round of letrozole and continue until it indicates you are ovulating. Doctors will usually prescribe letrozole for a total of three to four cycles before determining the medication failed.
Letrozole (Femara®) side effects
Since letrozole lowers a person’s estrogen levels, there will naturally be side effects. The most common effects reported are: bloating, blurred vision, breast swelling and tenderness, difficulty sleeping, dizziness, fatigue, nausea, and headaches. Some individuals reported the medication increased their anxiety and caused mood swings and irritability. Others reported hot flashes, night sweats, and spotting.
In rare circumstances, people taking letrozole can develop ovarian hyperstimulation syndrome (OHSS), which causes bloating, digestive issues like diarrhea, and even shortness of breath and chest pains. Similarly, ovarian cysts may appear and cause pain or pressure on one’s pelvis with any type of exertion, including intercourse. However, ovarian cysts will typically resolve on their own and won’t require additional treatment.
It’s also important to consider the effects of letrozole on pregnancy and chestfeeding. Your doctor will most likely require you to have a negative pregnancy test prior to beginning the medication. Given the short duration one is typically using letrozole, the medication will leave your system and not harm your new pregnancy.
Average success rates with Letrozole
First, in order to determine whether you’re a candidate, your physician will need to know whether your periods are irregular and how often you miss your period for unexplained reasons. For individuals with regular periods but unexplained infertility, they’ll also check to see if your progesterone levels are low. Other blood tests that might be done before prescribing letrozole will check your thyroid and prolactin levels and blood sugar for signs of diabetes.
You’ll also undergo AMH testing to determine your egg reserve because if your AMH is too low, letrozole is unlikely to improve your chance of getting pregnant. Additionally, if you’re using a partner’s sperm or a known-donor, your doctor will want to determine their sperm count to be sure that is not an issue. The reason for the thorough testing is because letrozole only addresses fertility problems related to ovulation and will not have an effect on other issues that may be making it difficult to conceive.
Those for whom letrozole is the right fit, there is evidence that it is more successful than Clomid. However, with any study and statistic, it’s important to remember that there are numerous factors which could lead to a pregnancy and healthy birth beyond medication.
A 2014 study from the New England Journal of Medicine found that 27.5% of people with PCOS who took letrozole had a successful birth compared to the 19.5% taking Clomid. The study also found that ovulation and live-birth rates were higher among infertile patients using letrozole, as opposed to patients prescribed Clomid as well as a higher birth rate among obese people with PCOS and fewer multiple pregnancies among people taking letrozole than Clomid. Another study, done in 2012, found that 25% of people taking letrozole had a live birth, whereas 16.8% of people taking Clomid had a live birth.
Letrozole vs. Clomid
Clomid has been the first-line treatment for treating ovulation-related infertility for many years. However, since doctors began using letrozole off-label (meaning, not its primary use according to the FDA) to treat infertility, there is some indication that letrozole has higher success rates, especially among specific populations, including older patients and those more prone to excessive weight gain.
Fertility specialists have also found that letrozole — not Clomid, despite previous assumptions — is of greater benefit to people with polycystic ovarian syndrome (PCOS). While the rates of ovulation and birth rates are not drastically different among people taking letrozole and others taking Clomid, there is a subtle advantage to using letrozole. The same 2014 study found that 2.5% of babies conceived using letrozole had congenital and chromosomal abnormalities, while nearly four percent of babies conceived with the help of Clomid did.
The main difference, however, between the two medications is that Clomid is prescribed at a higher dosage, starting at 50mg, as opposed to 2.5mg of letrozole. Additionally, Clomid can be used to help male-factor infertility by increasing sperm count and motility.
Other uses for Letrozole
The primary use of letrozole is in combination with surgery, chemotherapy, and radiation to treat and prevent the recurrence of hormone-receptor positive breast cancers. It may also be used as a treatment for early-stage breast cancer in people who already experienced menopause or people who went through menopause and were treated with the drug tamoxifen for at least five years.
That more fertility specialists are exploring infertility treatments beyond Clomid, which has been used for more than 20 years, is a hopeful sign for people experiencing infertility. Understanding how different medications can interact with the body will lead doctors and researchers to determine how best to help someone conceive and have a healthy pregnancy and birth. Now, if one medication or method doesn’t work, people can explore alternatives that are seeing similar, if not greater, rates of conception.
As always, we encourage you to bring your questions about the different options available to your doctor so, together, you can map out the best (for you) plan to conceive. And remember — what is best for you might not be the same for someone else. The best approach to fertility support is one with an open mind. If we can support you in any way, please do reach out. We are here to help as best we can!