Clomid vs. Letrozole: Which Fertility Pill Is Better?

At a glance

What the evidence says

A large randomized trial published in the New England Journal of Medicine in 2014 compared the two in people with PCOS and found that letrozole produced more live births than clomiphene. Many specialists now use letrozole first for PCOS. For unexplained infertility, both are used, often together with IUI, and evidence is more mixed.

How to choose

• PCOS: letrozole is commonly preferred.
• History of a thin lining or poor mucus on clomiphene: letrozole may be suggested.
• Cost and access: both are inexpensive generics, though prescriptions and monitoring costs differ.
• Side effects: a person who has not tolerated one may do better with the other.

Safety and monitoring

Ultrasound monitoring helps ensure you do not have too many mature follicles, which lowers the chance of high-order multiples. Do not use either if you might be pregnant unless instructed. Tell your clinician about all medicines and supplements.

When pills are not enough

If you have not conceived after a few ovulatory cycles, your clinician may suggest gonadotropin injections, IUI or IVF. See ovulation induction.

Questions to ask

Which medication is right for me, and why? How will ovulation be confirmed? How many cycles before we reconsider? What is my chance of twins? Add them to your appointment questions.

How doctors choose in practice

Beyond the trial data, clinicians look at your history. If you have PCOS, letrozole is increasingly the default. If you have taken clomiphene before and ovulated but not conceived, they may switch, particularly if there are signs that the lining or mucus were affected. If you cannot tolerate one, the other may be easier. Cost and local availability matter little, as both are inexpensive, but insurance rules and prescriber habits do shape which one you get first.

Experience of side effects

People often describe clomiphene as stirring mood swings, hot flashes and, for some, a “crazy” feeling, while many describe letrozole as milder, with tiredness and headaches. Experiences vary widely. Keep a short note of how you feel each day of a cycle, to share with your prescriber, and tell them if side effects are severe.

Dosing and cycle length

Both start at low doses and may be increased. Cycle length may shift. With either, ovulation often falls later than in a natural cycle, so LH testing or ultrasound helps time intercourse. If ovulation occurs at a certain dose and you do not conceive, ask whether to try the same dose again or change.

Combining with IUI

Both medications are often paired with IUI, which can increase the chance of pregnancy per cycle compared with medication and timed intercourse alone in some groups. Ask whether this suits your diagnosis.

When neither works

If you do not ovulate at the highest reasonable dose, if you ovulate but do not conceive after several cycles or if side effects are intolerable, your clinician may move to gonadotropins, IUI or IVF. Moving on is a normal part of treatment, not a failure.

Safety messages

Never use leftover medication from someone else, and never take either medicine without checking that you are not pregnant. Report severe pelvic pain, vision changes or breathlessness. Both medicines require medical supervision. If you are considering ordering from an online source, check that it requires a prescription and a clinician review. See online fertility programs.

Frequently asked practical questions

Can I take it in the evening? Many people take the tablets at the same time each day, often with food, as directed. Does it matter which cycle days I start? Your clinician will specify, often cycle day 3 to 5, and some use day 2 to 6. What if my cycle is very long? You may need medication to induce a bleed first, since the start date is counted from a period or induced bleed. Will it cause hot flashes? Possibly, and they pass after the cycle. Can I exercise? Light to moderate exercise is usually fine, but ask about activity if you have large ovarian cysts. How soon will I know? A pregnancy test about two weeks after ovulation will tell you, and your clinic may arrange blood tests earlier.

Why monitoring is worth the effort

Without monitoring, you cannot know whether you ovulated, how many follicles developed or whether the dose is right. Monitoring helps you avoid wasted cycles, and reduces the chance of twins. If cost is a barrier, ask your clinic about the minimum monitoring that is safe, and consider using ovulation tests at home in addition. See ovulation induction.

More detail

Read the full guide to clomiphene and letrozole.