LAS VEGAS -- Aromatase inhibitors may be the answer for women in whom clomiphene fails to induce ovulation, Dr. Robert F. Casper said at the Fifth World Congress on Controversies in Obstetrics, Gynecology, and Infertility.
Studies have suggested that the aromatase inhibitor letrozole is at least as effective as clomiphene in inducing ovulation in women with polycystic ovary syndrome (PCOS) and is associated with a higher clinical pregnancy rate and fewer multiple pregnancies, said Dr. Casper of the division of reproductive sciences, Mount Sinai Hospital, Toronto, and the University of Toronto.
Other studies have shown that combining an aromatase inhibitor with FSH injections can induce ovulation, decrease the FSH dose needed for ovarian stimulation, and enhance fertility in women undergoing treatment for idiopathic infertility.
Aromatase inhibitors--letrozole, arimidex, and exemestane--have been associated with a decline in blood and tissue levels of estrogen to as low as menopausal levels in some patients.
Dr. Casper and his associates hypothesized that administration of an aromatase inhibitor early in the menstrual cycle would mimic the central action of clomiphene without depleting estrogen receptors. The ensuing decrease in circulating estrogen would diminish the negative feedback on FSH, resulting in higher FSH levels, stimulation of follicle development, and ovulation.
In an observational, pilot cohort study, Dr. Casper and Dr. Mohamed Mitwally offered combination therapy with letrozole plus FSH to 12 women with unexplained infertility who had a poor response to at least two cycles with FSH alone, defined as no more than two follicles at least 1.8 cm in diameter on the day of the luteinizing hormone surge or HCG administration.
The patients received 2.5 mg of letrozole per day from day 3 through day 7 of their menstrual cycles, plus 50-225 IU of FSH per day on days 5-7. When at least two follicles were 2 cm or more in diameter, 10,000 IU of HCG were administered, followed by intrauterine insemination (Fertil. Steril. 77:776-80, 2002).
Together, the women underwent a total of 20 completed cycles with FSH alone and 14 cycles with combination treatment.
The mean number of mature follicles produced during treatment with letrozole plus FSH was 3.3, significantly more than the 1.9 obtained during treatment with FSH alone. Four pregnancies occurred during the letrozole-FSH regimen, compared with none during the FSH-only regimen.
Ovulation induction is still considered an off-label use for aromatase inhibitors. Dr. Casper pointed out that in at least one study, women who received clomiphene and FSH had a significant decrease in endometrial thickness on the day of HCG administration, and their pregnancy rate was 11%, significantly less than the 22% rate achieved by women who received FSH alone. Still, these drugs may have value for some infertile patients and further study is warranted, Dr. Casper said.
BY NORRA MACREADY
Los Angeles Bureau
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