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Follicular Phase Dynamics with Combined Aromatase Inhibitor and Follicle Stimulating Hormone Treatment

Reproductive Sciences Division, Department of Obstetrics and Gynecology, University of Toronto, Toronto, Canada M5G 1X5

Address all correspondence and requests for reprints to: Robert F. Casper, M.D., Division of Reproductive Sciences, Fran and Lawrence Bloomberg Department of Obstetrics and Gynecology, University of Toronto, and Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Room 876, Toronto, Ontario, Canada M5G 1X5. E-mail: RFcasper{at}aol.com.

Objective: The objective of this study was to evaluate follicular phase parameters during ovarian stimulation with FSH alone or with the aromatase inhibitor letrozole.

Methods: Two groups of women undergoing intrauterine insemination (IUI): group I (389 patients; mean age 35 ± 4.3 yr) underwent 630 IUI cycles stimulated with letrozole and FSH; and group II (134 patients; mean age 36.0 ± 4.6 yr) underwent 166 IUI cycles stimulated with FSH only. Each group was stratified into ovulatory and anovulatory cycles. Patients were monitored by ultrasound for folliculometry and blood sampling for hormonal assay on d 3, 7, 9, or 10 of the cycle, and on the day of human chorionic gonadotropin administration.

Results: Group I had a significantly lower follicular count greater than 10 mm on d 7, greater than 12 mm on d 9 or 10, and greater than 15 mm on the day of human chorionic gonadotropin administration compared to group II (P = 0.006, <0.001, and <0.001, respectively). After stratifying patients by diagnosis, this relationship was maintained only for patients with ovulatory infertility (P = 0.003, <0.001, and <0.001, respectively). Serum estradiol (E2) was significantly lower in the group I ovulatory and anovulatory at the last three monitoring visits (P < 0.001). However, the difference in E2 levels decreased in the preovulatory period with similar E2 levels per mature follicle. No premature preovulatory progesterone rise was observed in either group. However, significantly lower progesterone levels were observed in the second half of the follicular phase in group I (P = 0.02 and <0.001). Endometrial thickness was significantly lower in group I at the second and third visits (P < 0.001, 0.01) but was comparable to group II at the last monitoring visit. Although, the pregnancy rates were similar between the two groups, the multiple pregnancy rate was significantly higher in the FSH-only group (P = 0.039).

Conclusion: The addition of letrozole modifies the follicular, hormonal, and endometrial dynamics of FSH-stimulated cycles with possible positive effects on the overall cycle outcome.