Single-Dose Letrozole Equal to Multiple-Dose Regimen in IUI


PHILADELPHIA — Patients with unexplained infertility who undergo ovarian stimulation before intrauterine insemination have comparable pregnancy rates and side effects when treated with a single 25-mg dose of letrozole, compared with five daily doses of 5 mg each, Marinko M. Biljan, M.D., reported.

“A single dose may be more practical and convenient for patients,” commented Dr. Biljan, medical director of the Montreal Fertility Centre, who reported his findings during the annual meeting of the American Society for Reproductive Medicine.

Letrozole, an aromatase inhibitor, was originally used for ovarian stimulation in infertility patients who responded poorly to clomiphene citrate or gonadotropin stimulation.

Dr. Biljan's previous work in this area has shown that, even in good responders to gonadotropins, letrozole used in combination with gonadotropins can reduce gonadotropin requirements by up to 50%.

Letrozole is considered by some specialists to be as effective as and possibly even superior to clomiphene for most patients undergoing intrauterine insemination (IUI).

But the traditional 5-mg dose starting at day 3 of the menstrual cycle and given through day 7 is often impractical, said Dr. Biljan, who now has experience with approximately 2,000 letrozole cycles.

“Patients would call us up and say they forgot their dose yesterday and [ask] should they take two doses today? It was becoming a problem,” he said.

Inspired by a pilot study of 7 patients who were treated with a single dose of letrozole and had similar responses to historical controls, Dr. Biljan launched his prospective, double-blind, randomized trial of 20 patients. The patients, all under age 40, had at least 12 months of unexplained infertility; they all had ovulatory cycles, patent tubes, and normal sperm parameters in their male partners.

The women in the study were randomized to receive either one 25-mg tablet of letrozole on day 3 of their menstrual cycle and a placebo pill on each of the next 4 days, or five daily tablets of 5-mg letrozole each.

“We were petrified of the possible side effects of such a large, single dose of letrozole, but in fact, there were actually more side effects reported in the women who took the smaller daily doses, although the difference was nonsignificant,” Dr. Biljan said.

A baseline transvaginal ultrasound scan was performed between days 1 and 3, along with a baseline blood test. These tests were repeated on day 9, after which daily scans were performed until the largest follicle reached a diameter of 18 mm.

Ovulation was then triggered with 10,000 U of β-hCG, and IUI was performed 36 hours later.

In addition to a similar rate of side effects, both groups had similar serum FSH and estradiol levels, similar numbers of follicles, and similar endometrial thicknesses.

Pregnancy rates were also similar, with two pregnancies in the single-dose group and one in the multi-dose group; this difference was not statistically significant.

Although he did not present the figures at the meeting, Dr. Biljan noted that he has now doubled the number of patients in his study and has achieved the same results.