Clomiphene Citrate / Letrozole
Clomiphene citrate (also known as Serophene®) is widely used as a first line treatment to induce and augment ovulation. Clomiphene citrate is an oral medication. Clomiphene Citrate is typically administered from days 3 to 7 of the menstrual cycle with day 1 being the first day of normal menstrual flow. The starting dose is usually 50 mg per day. If ovulation is not achieved at this dose, the dose can be gradually increased by 50 mg per cycle till ovulation occurs. The effective dose of clomiphene citrate varies from individual to individual. Ovulation usually occurs 5-8 days after the last tablet is taken. Couples are advised to have intercourse every other day during this time. Clomiphene citrate is also given to augment ovulation to optimize the success rate of intrauterine insemination.
Early in treatment, it is common for patients to take clomiphene citrate for 5 days each month and have blood drawn for a progesterone level on day 24 of their cycle to monitor for ovulation. This permits the dosage to be titrated appropriately. In some situations the physician may wish to monitor the cycles more closely by utilizing ovulation predictor kits and/or ultrasounds. This provides additional information on the number of developing follicles and their rate of growth. A number of patients may not be able to detect spontaneous ovulation despite follicular development. In such case, ultrasound monitoring (also known as follicular tracking) allows us to pinpoint the optimal timing so ovulation can be triggered artificially by the administration of a medication called HCG (Chorionic Gonadotropin®).
Clomiphene citrate has been used since 1960 and is considered a safe and effective medication. Side-effects of clomiphene citrate may include abdominal discomfort, hot flashes, vaginal dryness, moodiness, headache and visual disturbances (see pharmacist product monograph for complete listing). Very rarely, clomiphene citrate can cause significant enlargement of the ovary a condition called ovarian hyperstimulation syndrome. Clomiphene citrate is associated with a 5-8% incidence of multiple births. The vast majority of these are twin pregnancies. There is no increased risk of birth defects with the use of clomiphene citrate versus the general population.
If clomiphene citrate has not produced a pregnancy within 3-6 cycles an alternate mode of treatment may be considered.
Check out our frequently asked questions (FAQ’s) for further information regarding clomiphene citrate.
Letrozole (also known as Femara®) is a medication manufactured for the treatment of breast cancer. However, studies have also shown letrozole can be effective for ovulation induction.
In 2005, the manufacturer of letrozole issued a contraindication for the the use of letrozole in women trying to conceive due to risk of fetal malformations. This initial reaction was based on a abstract of 150 babies born to women using letrozole. Subsequently, multiple large, quality studies have demonstrated no increased risk of fetal malformations versus the general population. Therefore, MotherRisk (a program based at Sick Kids Hospital which monitors drug safety in pregnancy) issued the following statement about letrozole in 2008:
“Based on the aforementioned findings, the use of letrozole to induce ovulation does not appear to be associated with an apparent increased risk of major congenital malformations in humans.”
The Canadian Fertility and Andrology Society (CFAS) and the Society of Obstetricians and Gynaecologists of Canada (SOGC) have released a Joint Position Statement on the use of letrozole for the management of infertility.
If you opt to go ahead with letrozole treatment, it is given orally usually in a dose between 2.5 to 7.5 mg from day 3 to 7 of the menstrual cycle with day 1 being the first day of normal menstrual flow. It is recommended to perform a pregnancy test prior to starting letrozole to ensure that this medication is not taken accidentally in pregnancy. If it is used to induce ovulation, the dose is titrated up each cycle to the dose required to achieve ovulation. A day 24 progesterone level will be used to confirm ovulation. Ovulation usually occurs 5-8 days after the last tablet is taken. Couples are advised to have intercourse every other day during this time. Letrozole is also given to augment ovulation and optimize the success rates of intrauterine insemination.
In some situations the physician may wish to monitor the cycle more closely by utilizing ovulation predictor kits and/or ultrasound evaluation. This provides further information on the number of developing follicles and their rate of growth. Occasionally, ovuation may be triggered by administration of a medication called HCG (Chorionic Gonadotropin®).
Side effects may include abdominal bloating, moodiness, dizziness, fatigue, headache and occasionally hot flashes or visual distrubances (see pharmacist product monograph for comple listing). Letrozole may very rarely cause significant ovarian enlargement and mild ovarian hyperstimulation syndrome. Letrozole is associated with a 5-7% incidence of multiple births. The vast majority of these are twin pregnancies
Letrozole may be used for up to 3 to 6 cycles and if pregnancy has not been achieved an alternate mode of treatment may be considered.