Last updated November 12, 2026 · Reviewed by the Gala Health team
Is letrozole approved for fertility?
No. The Femara (letrozole) label lists three indications, all for breast cancer in postmenopausal women. Prescribing an approved medicine for a different use is legal and common, and it is called off-label use.
Professional guidance supports this particular off-label use. The 2023 International Evidence-based Guideline for PCOS recommends letrozole as the first-line drug treatment for ovulation induction in infertile women with PCOS who do not ovulate and have no other infertility factors, and recommends it over clomiphene to improve ovulation, clinical pregnancy and live birth. ACOG's Practice Bulletin on PCOS (No. 194, reaffirmed in 2025) carries an interim update reflecting the same evidence on letrozole.
The guideline also asks clinicians to tell women when an ovulation-induction drug is off-label and to discuss the evidence, possible concerns and side effects. Expect that conversation before a prescription.
Who letrozole is for
Letrozole works by prompting ovulation, so it helps when the problem is that ovulation is not happening regularly, most often because of PCOS. It does not open a blocked tube or fix a low sperm count. That is why the guideline's recommendation is limited to women with "no other infertility factors", and why the large PCOS trial behind it only enrolled women with at least one open fallopian tube, a normal uterine cavity and a male partner with a sperm concentration of at least 14 million per milliliter.
Beyond PCOS, ASRM's guideline on unexplained infertility evaluated oral treatments, including aromatase inhibitors, and concluded that treatment of unexplained infertility is by necessity empiric. In other words: find out what is going on in both partners first, then choose.
This is the reason a couple's workup comes before a prescription in Gala Fertility: her hormones and ultrasound, and his semen analysis, are what tell a clinician whether letrozole fits.
Letrozole dosage and timing in the studies
Doses for fertility come from trials, not from the label. In the 2014 PPCOS II trial in the New England Journal of Medicine, it was used like this:
| Step | In the PPCOS II trial |
|---|---|
| Start of the cycle | After a natural period, or a withdrawal bleed brought on by medroxyprogesterone 5 mg a day for 10 days |
| Starting dose | 2.5 mg a day (one tablet) on cycle days 3 to 7 |
| If she did not ovulate | The dose was raised in the next cycle, judged by a midluteal progesterone below 3 ng/mL |
| Highest dose | 7.5 mg a day (three tablets), still for 5 days |
| How long | Up to five treatment cycles |
The Femara label says letrozole is taken without regard to meals and does not set a time of day, so morning or night is a matter of habit. Its elimination half-life is about 2 days.
In Gala Fertility, a cycle on letrozole or clomiphene is one tablet a day for 5 days, on days 3 to 7, prescribed one month at a time. Your clinician sets the dose and adjusts it at the check-in after each cycle.
How well letrozole works: the PPCOS II numbers
The trial randomly assigned 750 women with PCOS, aged 18 to 40, to letrozole or clomiphene. The results, for the whole group:
| Outcome | Letrozole | Clomiphene |
|---|---|---|
| Live birth (cumulative) | 27.5% (103 of 374) | 19.1% (72 of 376) |
| Ovulation (share of treatment cycles) | 61.7% | 48.3% |
| Pregnancy loss | 31.8% of pregnancies | 29.1% of pregnancies |
| Twin pregnancy | 3.4% | 7.4% |
Live birth and ovulation were significantly higher with letrozole. The differences in pregnancy loss and twins were not statistically significant, and neither was the difference in major congenital anomalies (four with letrozole, one with clomiphene).
These figures describe women with PCOS who met strict entry criteria and had their cycles tracked. They are not a forecast for any one couple, and they do not apply to women who already ovulate regularly.
Side effects of letrozole for fertility
In PPCOS II, letrozole caused more fatigue and dizziness than clomiphene, while clomiphene caused more hot flushes. Rates of other adverse events were similar between the two.
The Femara label warns that fatigue, dizziness and somnolence may occur and advises caution when driving or operating machinery. Its longer list of common reactions, led by hot flashes and joint pain, comes from women with breast cancer taking it every day for years, not for 5 days a month.
Questions such as weight gain, hair loss or mood changes on a 5-day course were not reported as differing in the trial. If something feels off during a cycle, tell your clinician at the check-in or by message.
Before you take it: pregnancy test and twins
- Pregnancy first. The Femara label contraindicates letrozole in pregnancy and asks for a pregnancy test before starting. The PCOS guideline says it should not be given where there is any possibility of an existing pregnancy, while noting no evidence of more birth defects than with other ovulation-induction drugs.
- Birth defects. The guideline states that current evidence shows no difference in fetal abnormality rates between letrozole, clomiphene and natural conception.
- Twins. Twin pregnancies were 3.4% on letrozole in PPCOS II, against 7.4% on clomiphene, a difference that was not significant. The trial's authors put the multiple-pregnancy rate with clomiphene at 3 to 8%, against under 1% without treatment.
- Prenatal vitamins. The guideline advises starting prenatal vitamins together with ovulation induction.
Monitoring: how you know it worked
The question each cycle is whether she ovulated. In PPCOS II that was judged by progesterone in the second half of the cycle. ASRM's committee opinion says a progesterone level above 3 ng/mL, drawn about a week before the next period is expected, is presumptive evidence that ovulation happened.
The PCOS guideline also asks for ongoing monitoring for adverse effects with any ovulation-induction drug. Whatever the method, the plan should change if a cycle does not work: a higher dose, a switch, or a referral.
How to get letrozole for fertility
Letrozole is a prescription medicine, so you need a clinician. The safe route is the one the guideline describes: confirm that ovulation is the problem and that there is no other infertility factor, which means testing both partners, then prescribe and follow each cycle.
That is how Gala Fertility works. You start with a $29.99 introductory video meeting with our care team. If you go ahead, both of you are tested: her bloodwork and pelvic ultrasound near you, his semen analysis with a kit at home. A clinician reviews every result with you on video and, only if it is right for you, prescribes letrozole or clomiphene one month at a time, shipped to your door, with a check-in after every cycle for up to six cycles. Medication is part of the plan, and the $29.99 is credited to your first cycle.
Comparing the two pills? Read letrozole vs. Clomid. Taking a GLP-1 such as Wegovy or Zepbound? Read trying to conceive on a GLP-1 first.
Frequently asked questions
How many mg of letrozole is used for fertility?
In the PPCOS II trial, women started at 2.5 mg a day for 5 days, and the dose was raised in later cycles up to 7.5 mg a day if they did not ovulate. Your clinician sets your dose.
What days do you take letrozole for fertility?
In the trial and in Gala Fertility, letrozole is taken once a day for 5 days, on days 3 to 7 of the cycle.
Does letrozole cause twins?
It can. In PPCOS II, 3.4% of pregnancies on letrozole were twins, against 7.4% on clomiphene; the difference was not statistically significant.
Can you take letrozole at night?
The Femara label says it can be taken with or without food and does not set a time of day. Pick a time you will remember for all 5 days.
Can you buy letrozole for fertility without a prescription?
No. Letrozole is a prescription medicine, and for fertility it should follow a workup of both partners. Gala Fertility prescribes it only when your clinician decides it is right for you.
Is letrozole better than Clomid for PCOS?
For women with PCOS who are not ovulating, the 2023 international PCOS guideline recommends letrozole over clomiphene, based on higher ovulation, pregnancy and live birth rates in trials such as PPCOS II.
Ready to talk to a provider?
Your answers go to a licensed provider, who decides whether treatment is right for you. Learn more about Gala Fertility.
More Gala Fertility guides
- AMH levels by age
- At-home semen analysis
- How long to try before fertility testing
- letrozole vs. Clomid
- Clomid prescription online
- trying to conceive with PCOS
- are at-home fertility tests accurate
- trying to conceive on a GLP-1
- male infertility causes
- fertility test cost
- does insurance cover fertility testing
- AMH test cost
- semen analysis cost
- best at-home fertility tests
- fertility insurance by state
Sources
- Legro RS, et al. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med. 2014.
- Teede HJ, et al. Recommendations from the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome. Fertil Steril. 2023.
- ACOG. Polycystic ovary syndrome. Practice Bulletin No. 194. 2018, reaffirmed 2025.
- Novartis / NLM DailyMed. Femara (letrozole) tablets prescribing information.
- Practice Committee of ASRM. Evidence-based treatments for couples with unexplained infertility: a guideline. Fertil Steril. 2020.
- Practice Committee of ASRM. Fertility evaluation of infertile women: a committee opinion. Fertil Steril. 2021.
This article is for general information and is not medical advice. Talk to a licensed provider about your own health.