Ovulation Induction - Letrozole |
                               
|
Letrozole is being used as an infertility treatment. It is the most recent addition to the drugs being used for fertility treatment. Fertility drugs are used often in infertility treatments. There are two situations in which fertility drugs may be useful. First, these drugs can be used to induce an egg to develop and be released in women who are not ovulating on their own. Fertility drugs can also be used to increase the chances of pregnancy in women who are already ovulating. Aromatase is an enzyme that is responsible for the production of oestrogen in the body. Letrozole is in a class of medications known as aromatase inhibitors. Letrozole works by inhibiting aromatase thereby suppressing estrogen production. Clomiphene citrate, on the other hand, blocks oestrogen receptors. In both cases, the result is that the pituitary gland produces more of the hormones needed to stimulate the ovaries. These hormones, FSH and LH, can cause the development of ovulation in women who are anovulatory or increase the number of eggs developing in the ovaries of women who already ovulate. As a result, several studies have now been published using letrozole as a fertility drug. By reducing oestrogen production the hypothalamus and pituitary increase their hormone production and this increases the stimulation to the ovaries. Clomiphene citrate lasts for a long time in the body and may therefore have an adverse effect on the cervical mucus and uterine lining. Letrozole is a medication that has been widely used in women with breast cancer. Recently, the manufacturer of Letrozole sent a notice to doctors warning that there are reported cases of birth defects that arose in the children of women who received Letrozole while pregnant. Novartis, the manufacturer of letrozole, reviewed their safety database and found 13 reports of pregnant women receiving the drug worldwide. Of those 13 women, two had children with birth defects. In the United States, the labeling of letrozole already warns that it has been associated with birth defects. Novartis has never sought FDA approval to market letrozole as a fertility medication and is clearly concerned about their liability if given in pregnancy. There are no reports of letrozole being associated with birth defects when given prior to pregnancy. It is important to make the distinction that when used as a fertility medication, letrozole is given before the establishment of 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. At least one major pharmaceutical company, Serono, is conducting studies with a similar medication called anastrozole in the hopes of obtaining FDA approval to market it specifically as a fertility medication. One of the earliest studies using letrozole as a fertility drug looked at 12 women with inadequate response to clomiphene citrate. Ovulation on letrozole occurred in 9 of 12 cycles and 3 patients conceived. A later study by the same investigators compared the effects of letrozole to those of clomiphene citrate. This time 19 women were studied. Ten women received clomiphene citrate and nine women received letrozole. This study was unable to demonstrate any difference in the number of women who ovulated, the number of eggs that developed in each woman, or the thickness of the uterine lining during treatment. However, a more recent study by a different group of investigators found that compared with clomiphene citrate, letrozole is associated with a thicker uterine lining and a lower miscarriage rate. Nobody has yet identified the optimal dose for letrozole. Three dose regimens have been tested: 2.5 mg, 5 mg and 7.5 mg. Different studies comparing these dose regimens have occasionally found favor with one dose or another but there is no conclusive data that one dose is better than another. The usual length of treatment is for five days. Some early studies suggested that the pregnancy rates with letrozole far exceeded those with clomiphene citrate and were possibly even higher than gonadotropins. Further data has determined that this is not the case. Pregnancy rates with letrozole are similar to those seen with clomiphene citrate and are lower than the pregnancy rates seen with gonadotropins. Older patients have a lower chance of success than younger patients. Treatment with letrozole may still be successful even if other treatments have failed. For example, some data shows that in women who did not ovulate with clomiphene citrate, they still may ovulate with letrozole. Letrozole side effects Letrozole works based on its ability reduce estrogen levels. Low estrogen levels of any cause can cause a woman to have symptoms. The data on side effects comes from women who have been using letrozole for an extended period of time in order to treat breast cancer. The treatment duration for letrozole is only five days. Side effects are similar to those seen with clomiphene citrate:
|
