Clomid/Letrozole + FSH Protocol

Combined Clomid/Letrozole + Injectable Gonadotropins (Gonal-F, Follistim, Repronex, Bravelle, Menopur

Clomiphene citrate (brand names - Clomid; Serophene), Letrozole (Femara), and human menopausal gonadotropins or recombinant FSH (FSH or HMG) (brand names - Humegon, Follistim, Bravelle, Gonal F, Repronex, Menopur) are medications used to stimulate ovulation.

Clomid citrate acts by stimulating production of FSH and LH from the pituitary gland. Letrozole acts at the level of the ovaries to stimulated pituitary production of FSH and LH as well.

Gonadotropins (FSH) act directly on the ovaries - these preparations contain follicle stimulating hormone (FSH) and/or luteinizing hormone (LH). These drugs are used in combination in some patients with normal ovulation to enhance their fertility and may be combined with IUI.

In this protocol, Clomid or letrozole is taken from the third through the seventh day of the menstrual cycle - day 1 being the first day of full flow. The usual dose is two tablets per day (Clomid-100 mg, Letrozole-5mg). Gonadotropins are given by subcutaneous injection on cycle day 9 - the usual dose is two ampules. An ultrasound to judge ovarian response is performed on day 12, 13, or 14. Human chorionic gonadotropin (HCG) is given, by injection, to stimulate release of the eggs.

Sometimes your doctor may adjust the dose of Clomid, letrozole, or the injectable gonadotropins up to a maximum of 150mg Clomid, 7.5mg of letrozole, or 3 days of injectable gonadotropins up to 3 ampules each day.

Side effects of Clomid can include: headache; abdominal fullness or bloating; hot flashes; blurred vision. These side effects are usually temporary and mild. There is no recognized risk incurred if these side effects are experienced. Similar side effects may occur with letrozole.

The FSH injection usually causes no side effects directly.

This combination drug therapy is highly effective in stimulating ovulation. Approximately 80% of women will ovulate normally. Pregnancy rates vary depending on other factors - sperm count, etc. When combined with IUI, for empiric therapy for couples who have infertility of unexplained origin, this protocol has approximately an 11-12% pregnancy rate.

There are two recognized risks of this therapy: Multiple pregnancy and ovarian cyst formation. Approximately 8% of Clomid or 11-12% of letrozole only conceptions are multiple - most are twins. This rate might be slightly higher with the combination of clomiphene and gonadotropins. Approximately 10% of women who are treated will develop an ovarian cyst. Again, this rate may be slightly higher with the addition of gonadotropins. For this reason, a pelvic ultrasound is performed at the end of each treatment cycle - around the time of menstrual period.

If an ovarian cyst is detected, treatment is withheld during the following cycle and the cyst usually resolves without further treatment. Complications of therapy including cyst rupture or ovarian torsion (twisting of the ovary cutting off the blood supply) are possible but extremely rare. If they occur surgery might be required.

There are medical studies in the early ‘90s suggesting that treatment with Clomid or gonadotropins may increase the long-term risk of developing ovarian cancer. There are also studies showing no link between these therapies and ovarian cancer. This is unsettled at this time. One study, related solely to the use of Clomid, suggests that the increased risk of ovarian cancer is incurred if treatment is conducted for 12 or more cycles.

Oral fertility drugs plus FSH have been in clinical use for over 25 years. There is a large amount of information suggesting that babies born as a product of this therapy are at a normal risk for congenital anomalies - not higher and not lower. There may be a slight increase in the risk of tubal pregnancy with this therapy. In addition there have been a variety of serious illnesses reported in association with clomiphene and with gonadotropin use. Their frequency is extremely rare and in many cases a proven link to clomiphene or gonadotropin is not clear.

The total cost of a treatment cycle is approximately $600-$850 assuming only one mid-cycle ultrasound is required (clomiphene 10 tablets – appx $18-$60; Letrozole 10 tablets – appx $75-$150; HMG or FSH - 2 ampules – appx $112-$196; HCG - 10,000 units – appx $60-$84; Vaginal sonography - $170.00 times 2 for your baseline ultrasound and mid cycle scan).

When combined with intrauterine insemination an additional $353.00 cost is incurred (sperm washing $228.00; IUI procedure $125.00). If you are not pregnant at the end of the cycle and menstrual bleeding starts, then you need to come in for another ultrasound (baseline) to assure there are no cysts remaining in your ovaries before you start another treatment cycle.