To use aromatase inhibition for induction of ovulation in women in whom clomiphene citrate (CC) treatment was unsuccessful.
Design
Prospective trial in infertility patients treated with CC.
Setting
Two tertiary-referral infertility clinics associated with the Division of Reproductive Sciences, University of Toronto.
PATIENT(S): Twelve patients with anovulatory polycystic ovary syndrome (PCOS) and 10 patients with ovulatory infertility, all of whom had previously received CC with an inadequate outcome (no ovulation and/or endometrial thickness of < or =0.5 cm).
INTERVENTION(S): The aromatase inhibitor letrozole was given orally in a dose of 2.5 mg on days 3-7 after menses.
MAIN OUTCOME MEASURE(S): Occurrence of ovulation, endometrial thickness, and pregnancy rates.
RESULT(S): With CC treatment in patients with PCOS, ovulation occurred in 8 of 18 cycles (44.4%), and all ovulatory cycles for the women included in this study had endometrial thickness of < or =0.5 cm. In 10 ovulatory patients, 15 CC cycles resulted in a mean number of 2.5 mature follicles, but all cycles had endometrial thickness of < or =0.5 cm on the day of hCG administration. With letrozole treatment in the same patients with PCOS, ovulation occurred in 9 of 12 cycles (75%) and pregnancy was achieved in 3 patients (25%). In the 10 patients with ovulatory infertility, letrozole treatment resulted in a mean number of 2.3 mature follicles and mean endometrial thickness of 0.8 cm. Pregnancy was achieved in 1 patient (10%).
CONCLUSION(S): Oral administration of the aromatase inhibitor letrozole is effective for ovulation induction in anovulatory infertility and for increased follicle recruitment in ovulatory infertility. Letrozole appears to avoid the unfavorable effects on the endometrium frequently seen with antiestrogen use for ovulation induction.
PMID 11172831 11172831 DOI 10.1016/s0015-0282(00)01705-2 10.1016/s0015-0282(00)01705-2
Cite this article
Mitwally, M. F., & Casper, R. F. (2001). Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate. Fertility and sterility, 75(2), 305-309. https://doi.org/10.1016/s0015-0282(00)01705-2
Mitwally MF, Casper RF. Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate. Fertil Steril. 2001;75(2):305-309. doi:10.1016/s0015-0282(00)01705-2
Mitwally, M. F., and R. F. Casper. "Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate." Fertility and sterility, vol. 75, no. 2, 2001, pp. 305-309.
The third-generation aromatase inhibitors were initially introduced to treat postmenopausal breast cancer. We now realize that many other potential indications for aromatase inhibitors exist, especially in the field of gynecology. Preliminary data were suggestive that aromatase inhibitors could be used to treat endometriosis and uterine leiomyomata and induce or augment ovulation.
Aromatase inhibitors promote ovulation, most likely by increasing endogenous FSH production owing to decreased estrogen biosynthesis in the ovary and extraovarian tissues, including the brain. Aromatase inhibitors differ from the estrogen antagonist clomiphene citrate in that they do not exert a direct unfavorable effect on endometrial growth and development during the menstrual cycle.
Healey et al. (1) report important findings on the effects of the addition of an aromatase inhibitor to gonadotropin injections for superovulation. A relatively large number of patients and a control group were studied, and several clinically useful outcomes including pregnancy rates were reported.
The addition of letrozole to an ovulation induction regimen using injectable gonadotropins in a mixed population of patients with infertility does not seem to offer any benefits over gonadotropin-only cycles, because the decreased gonadotropin dose (the only apparent benefit) was offset by increased complexity of the treatment. Further randomized clinical trials using a similar design and patient sample may not provide clinically useful data. On the other hand, optimization of this regimen (gonadotropin plus aromatase inhibitor) in poor responders may offer an alternative in this subset of women (2).
From the existing literature, it appears that use of an aromatase inhibitor alone to induce or augment ovulation will continue to be an exciting area of research future (3, 4). In particular, the dosing and timing of administration (late luteal versus early follicular) of an aromatase inhibitor for ovulation induction should be optimized. Defining the hormonal profiles of the women who will benefit the most from aromatase inhibition may further increase the success of treatment.
In summary, Healey et al. (1) should be congratulated for conducting this interesting work. Carefully designed randomized studies on the use of aromatase inhibitors for ovulation induction or augmentation are warranted.