Which Is Better for Unexplained Infertility, Letrozole or Clomid?


Woman reading pamphlet about Clomid | RSC SF Bay Area | CA

Infertility can be a confusing diagnosis but adding in all the fertility medications complicates the process even more.

So you’re about 15 minutes into your first visit with the fertility specialist and he or she starts talking to you in a foreign language, with words like clomiphene citrate and letrozole.

Your mind may already be spinning trying to remember if you really did time all those cycles correctly and if your ovulation kit test was truly 14 days before your last menstrual period. And now some new medication vocabulary! Egad!

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What are these fertility drugs and what do they do?

It has now become clear that letrozole is the medicine of choice if you do not ovulate. Women with PCOS (polycystic ovary syndrome) who need help ovulating tend to have the best success when using letrozole with timed intercourse in order to achieve a live birth. But if you are already ovulating and you’ve been diagnosed with unexplained infertility, the doctor may be talking to you about options that include letrozole or Clomid (brand name for clomiphene citrate) compared with the option to go directly to in vitro fertilization (IVF).

Related Reading: Clomid & Fertility Drugs

For many of you, your doctor rather than you, will make the decision of whether you should take letrozole or Clomid. However, it’s important to be informed of the differences so that you’re educated about your own medical care.

Both letrozole and clomiphene citrate are used for ovulation induction (causing someone to ovulate). But many people who are given one of these medicines are already ovulating. So, what is their purpose, then? Enhancing ovulation and conception.

We know from randomized controlled studies that using an ovulation induction agent in combination with intrauterine insemination brings about a greater success rate when using the pills alone or doing insemination without the pills. It’s the combination that seems most helpful.

Then, how are letrozole and Clomid different?

They are different in the mechanism in which they induce ovulation. Letrozole lowers your estrogen during the five days of administration by blocking the aromatase inhibitor enzyme. Clomid also lowers estrogen, but does so by blocking the receptor in the brain.

Clomid tends to make the uterine lining thinner and cervical mucus thicker in some patients. Clomid also has more side effects, which include hot flashes (31%) and constipation (9%). Letrozole tends to cause more joint pain (6%). Both medicines cause abdominal bloating (17%-18%) and headache (35%-40%).

One of the most recent systematic reviews and meta-analysis by Dr. Ashley Eskew revealed that the pregnancy rates were quite similar between these two medicines. Additionally, twin gestation and spontaneous miscarriage were also similar.

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Estrogen levels were slightly lower in the letrozole group, which is especially important for women with endometriosis or a prior history of estrogen sensitive cancer. Low dose letrozole of 2.5 mg appeared to have the highest success per cycle compared with Clomid (20% vs. 13%), although further studies are needed to determine the best dose for an individual patient. Most clinics use 5 mg of letrozole daily.

Both medicines tend to be covered by insurance at equal rates and also cost similar amounts for most pharmacies if there is not insurance coverage. Neither medicine should be taken unless you’re absolutely certain you’re not currently pregnant. This usually means you should do a home pregnancy test or blood pregnancy test prior to initiating medicine.

So now you have the facts: both medicines can be successful, but they have slightly different side effect profiles.