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letrozole ovulation day

Letrozole for Superovulation

Letrozole is an oral fertility medication.  It can be used to induce ovulation in women who don’t ovulate, or to produce multiple eggs in women who already ovulate on their own.  It is an alternative medication for those who have experienced significant side effects with clomiphene citrate (hot flashes, mood swings, thinning of the endometrium).  The two medications are comparable in terms of ovulation rates, pregnancy rates and risk of multiple pregnancies.

Letrozole may have harmful effects upon a developing pregnancy, and a negative blood pregnancy test is required before starting each cycle of medication.  Depending upon your situation, the doctor may request that you get a baseline ultrasound performed before you start therapy.  If so, call the office (913)780-4300 when your period begins. The ultrasound is generally scheduled on the second or third day of your period.

You will take two tablets (5 mg total) of letrozole daily, starting on Cycle Day 3 (the first day of menses is Cycle Day 1) and ending on Cycle Day 7.  You can take the two pills together, and the time of day is not important (just be consistent for the five days). 

When is letrozole used for ovulation induction?

Letrozole can be used in patients working on getting pregnant with PCOS (or polycystic ovary syndrome) who have irregular or absent period.

Letrozole can be used as an alternative in women who develop a thin uterine lining on clomiphene citrate. Unlike clomiphene citrate, with letrozole there is no blockage of estrogen receptors and the uterine lining and cervical mucus are not affected.

Letrozole can be used in combination with fertility injections (gonadotropins) for IVF. This is especially so in patients with estrogen sensitive cancers where high E2 levels are to be avoided (see above).

Letrozole has also been used in poor responder patients along with high doses of gonadotropins.

How effective is letrozole?

Togas Tulandi, a reproductive endocrinology and infertility specialist and chief of the obstetrics and gynaecology department at the McGill University Health Centre in Montreal, says that letrozole has a decent rate of inducing ovulation. The same 2014 study from the New England Journal of Medicine showed that, among participants with PCOS who used letrozole, 27.5 percent got pregnant within five cycles and went on to have live births. The study also found that the drug induced ovulation in 61.7 percent of women with PCOS.

What is the usual dose of Letrozole?

The usual starting dose is 2.5 mg orally daily without regards to meals. It is usually given for 5 days starting on cycle days 2, 3, 4 or 5. The daily dose can be increased to 5 or 7.5 mg if needed.

Side Effects

Letrozole works by reducing estrogen levels in order to stimulate ovulation. Low estrogen levels of any sort can cause a woman to have symptoms. Those most commonly seen with Femara use include:

  • Fatigue
  • Dizziness
  • Headache
  • Bloating
  • Hot flashes
  • Night Sweats
  • Blurred vision
  • Upset stomach
  • Breast pain
  • Difficulty sleeping

Letrozole and birth defects

A study presented at ASRM in 2005, in which researchers analyzed births that occurred after treatment with letrozole found seven serious birth defects in 150 babies, which is about 4.7%. This was compared to a database of 36,050 normal deliveries. The incidence of birth defects in the control babies was 1.8% This means that birth defects were 3 times more likely to occur with letrozole.

This prompted the manufacturer (Novartis) to review their safety database and found 13 reports of already pregnant women receiving the drug worldwide. Of those 13 women, two had children with birth defects (15.4%).Novartis sent a letter to fertility physicians stating: “Femara (letrozole) is contraindicated in women with premenopausal endocrine status, in pregnancy, and/or lactation due to the potential for maternal and fetal toxicity and fetal malformations”.

In response, 5 Canadian fertility centers reviewed their birth outcomes and incidence of birth defects in women who conceived with letrozole and compared them to Clomid. The Canadian study involved 911 newborns. The major birth defect rate in the letrozole group was 1.2% (6/514) and in the Clomid group was 3.0% (12/397).

In the United States, the labeling of letrozole already warned that it had been associated with birth defects. Novartis has never sought FDA approval to market letrozole as a fertility medication and was clearly concerned about their liability if given in pregnancy.

Letrozole is a medication that is metabolized rapidly in the body. It is not thought to have significant levels in the blood or tissues for a prolonged period of time.

In the PPCOS II study, each baby born was closely studied for birth defects at the time of birth with additional screening within 1 month of birth by trained pediatric personnel. There was no difference in the rate of birth defects between letrozole and Clomid.

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