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Journal of the Society for Gynecologic Investigation
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Aromatase Inhibition Reduces the Dose of Gonadotropin Required for Controlled Ovarian Hyperstimulation

Mohamed F. M. Mitwally, MD

Reproductive Sciences Division, Department of Obstetrics and Gynecology, University of Toronto, Toronto, Canada; Department of Gynecology and Obstetrics, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York (SUNY), Buffalo, New York

Robert F. Casper, MD

Reproductive Sciences Division, Department of Obstetrics and Gynecology, University of Toronto Room 876, Samuel Lunenfeld Research Institut, Mt. Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada, M5G 1X5 RFCasper{at}aol.com

Objective: To compare the use of the aromatase inhibitor, letrozole, in conjunction with follicle-stimulating hormone (FSH) injection, and FSH alone for controlled ovarian hyperstimulation (COH) in patients with polycystic ovarian syndrome (PCOS) or ovulatory infertility.

Methods: This nonrandomized study included two study groups: 26 patients with PCOS and 63 with ovulatory infertility (unexplained infertility [41 patients], male factor infertility [17 patients], and endometriosis [5 patients]), who received letrozole in addition to FSH; and two control groups: 46 PCOS patients and 308 with ovulatory infertility (unexplained infertility [250 patients], male factor infertility [42 patients], and endometriosis [16 patients], who received FSH only. All patients had intrauterine insemination (IUI). Main outcome measures included dose of FSH used per cycle, number of preovulatory follicles greater than 16 mm in diameter, cancellation rate, and pregnancy rate.

Results: The FSH dose required for ovarian stimulation was significantly lower when letrozole was used in both study groups comparedto the control groups without a significant difference in number of follicles greater than 16 mm. IUI cancellation rate was significantly lower with letrozole treatment in PCOS patients. In women with PCOS, clinical pregnancy rate per completed IUI cycle was 26.5% in the letrozole plus FSH group versus 18.5% in the FSH-only group. In ovulatory infertility patients, the pregnancy rate was similar in both study and control groups (11%).

Conclusion: We believe that inhibition of estrogen synthesis by aromatase inhibition will release the estrogenic negative feedback, resulting in an increase in endogenous FSH secretion. Moreover, by inhibiting conversion of androgens into estrogens, accumulating androgens may increase follicular sensitivity to FSH. Such a protocol has the potential to lower FSH treatment cost and may improve response for low responders who require high FSH doses during ovarian stimulation.

Key Words: Aromatase inhibitors • letrozole • polycystic ovarian syndrome • infertility • ovarian stimulation

Journal of the Society for Gynecologic Investigation, Vol. 11, No. 6, 406-415 (2004)
DOI: 10.1016/j.jsgi.2004.03.006


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