Clomiphene and Letrozole: Oral Ovulation Medications

What are oral ovulation medications?

Clomiphene citrate and letrozole are pills used to help people who do not ovulate regularly, or who have unexplained infertility, release an egg. They are usually the first medicines tried in ovulation induction because they are inexpensive, taken by mouth and carry a lower risk of high-order multiples than injectables.

How they are taken

A typical course is one tablet daily for five days starting on cycle days 3 to 5, though your clinician will decide the dose and timing. Ultrasound or ovulation (LH) tests may be used to confirm ovulation, and intercourse or IUI is timed accordingly, sometimes with a trigger shot.

Clomiphene

Clomiphene is the longest-used option and is FDA-approved to treat ovulation problems. It can cause hot flashes, headaches, mood swings and, uncommonly, visual changes (stop and call your clinician). Because it can have an anti-estrogen effect on the lining and cervical mucus, it sometimes lowers the chance of implantation even when ovulation occurs.

Letrozole

Letrozole is approved for breast cancer and is widely used off-label for ovulation induction. In a large randomized trial in people with PCOS, letrozole led to more live births than clomiphene. It has a shorter half-life and less anti-estrogen effect on the lining. Side effects may include fatigue, dizziness and hot flashes. Compare them in Clomid vs. letrozole.

Monitoring and risks

• Multiple pregnancy. Twins are more likely than with natural conception. Ultrasound monitoring helps limit the number of mature follicles.
• Ovarian cysts may form and usually resolve on their own.
• Not for pregnancy. Do not take these medicines if you might be pregnant unless instructed.

Who should not use them

Oral medications are not helpful if the tubes are blocked, if there is severe male factor infertility or if ovarian reserve is very low. A clinician should review your history, thyroid and prolactin results and other tests first. See fertility testing.

Questions to ask your prescriber

Why this medication for me? What dose and for how many cycles? How will ovulation be monitored? What is the chance of twins? When will we move on if it does not work?

A typical medicated cycle, day by day

Your clinician will give you exact instructions, but a typical oral cycle looks like this. You call the clinic on the first day of full flow. Between cycle day 2 and 5 you start the tablets and take them for five days. Around cycle day 10 to 14 you may have an ultrasound, or begin ovulation tests. If a follicle is mature, intercourse or IUI is timed, sometimes with a trigger shot. About a week after ovulation, a blood test may confirm that you ovulated. Two weeks after ovulation, you take a pregnancy test. If your period comes, you start again, often with a higher dose.

Dose adjustments and what they mean

Starting doses are low, and many clinics raise the dose in later cycles if ovulation does not occur. Higher doses may increase side effects and, for clomiphene, the anti-estrogen effect on the lining. A cycle with no ovulation is useful information, not a waste, since it helps to find the right dose. If you ovulate at a dose but do not conceive after a few cycles, it is usually better to change the plan than to keep repeating it.

Interactions and safety checks

Tell your prescriber about all medications and supplements, including herbal products. Letrozole is metabolized in the liver, so liver conditions matter. Clomiphene should not be used if you have unexplained abnormal bleeding or certain ovarian cysts. Vision changes with clomiphene, such as blurring or spots, are a reason to stop and call. Neither medicine is meant for use during pregnancy, so test if your period is late before starting a new cycle.

Ovarian cysts

Small functional cysts can form after ovulation induction and usually go away. They may delay the next cycle. Your clinician may check with ultrasound before starting again.

Using these medications for men

Clomiphene is sometimes prescribed to men with low testosterone and low sperm production because it raises the body’s own hormone signals. It differs from testosterone replacement, which suppresses sperm. This use is off-label and needs a urologist or endocrinologist’s guidance. See male factor infertility.

Costs and where to get them

Generic tablets are inexpensive at most pharmacies. The larger expense is usually monitoring. Ask whether your plan covers ultrasounds and bloodwork when billed for infertility, and compare pharmacy prices. See fertility costs and insurance.

When it does not work

If you do not conceive after several ovulatory cycles, review the whole picture rather than repeating the same step. Ask whether tubes have been checked, whether the partner has had a semen analysis, whether the lining and cervical mucus could be affected by clomiphene, and whether your age changes the pace. A switch to letrozole, the addition of IUI or a move to injectables or IVF may be appropriate. It also helps to ask for a written plan with checkpoints, so that each cycle has a purpose and months are not lost to drift.

Online prescribing

Some online fertility programs prescribe ovulation medication after testing both partners. Read our Gala Fertility review and online fertility programs.