Kilic-Okman, T., Kucuk, M., & Altaner, S. (2003). Comparison of the effects of letrozole and clomiphene citrate on ovarian follicles, endometrium, and hormone levels in the rat. Fertility and sterility, 80(6), 1330-1332. https://doi.org/10.1016/j.fertnstert.2003.05.002
Kilic-Okman T, Kucuk M, Altaner S. Comparison of the effects of letrozole and clomiphene citrate on ovarian follicles, endometrium, and hormone levels in the rat. Fertil Steril. 2003;80(6):1330-1332. doi:10.1016/j.fertnstert.2003.05.002
Kilic-Okman, Tulay, et al. "Comparison of the effects of letrozole and clomiphene citrate on ovarian follicles, endometrium, and hormone levels in the rat." Fertility and sterility, vol. 80, no. 6, 2003, pp. 1330-1332.
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To compare the effects of letrozole and clomiphene citrate in the rat in terms of number of ovarian follicles; endometrial thickness; and serum levels of E2, FSH, LH, and T.
Design
Controlled prospective study.
Setting
University research laboratory.
Animals
Thirty sexually mature female Wistar-Albino rats that were 20 weeks of age.
Interventions
Letrozole, 5 mg/kg of body weight daily (10 rats); clomiphene citrate, 100 microg/kg daily (10 rats); or saline solution, 2 mL/d (10 rats). After 2 days, rats were euthanized and ovariectomized.
Main Outcome Measures
Number of mature follicles, endometrial thickness, and serum levels of hormones.
Results
Mean levels of FSH, LH, E2, and T; number of mature follicles; and ovary size differed among the groups, whereas the mean endometrial thickness did not differ.
Conclusions
In rats, the effect of letrozole on follicular maturation is similar to that of clomiphene citrate.
To use aromatase inhibition for induction of ovulation in women in whom clomiphene citrate (CC) treatment was unsuccessful. Prospective trial in infertility patients treated with CC. 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.
Fifteen ovulating women had serial ultrasound scans to measure follicular, endometrial, and uterine growth, as well as biochemical indices including estradiol (E2) and the free androgen index, throughout a natural and a clomiphene-citrate-induced cycle. Despite higher E2 levels in the 5 days preceding ovulation, the clomiphene cycles were characterized by absence of the normal increase in uterine volume and an inhibition of endometrial thickening. It is proposed that the anti-estrogen effect of clomiphene inhibits the normal cyclical growth of the uterus and endometrium.
To investigate whether the timing of administration of clomiphene citrate (CC) affects hormone levels, follicular recruitment, reproductive end organs, and pregnancy rates. Prospective, randomized, double-blind trial. Academic center. PATIENT(S): Twenty-three patients with unexplained infertility. INTERVENTION(S): Twenty-three patients with unexplained infertility underwent 45 cycles of CC and IUI. For each cycle, patients were randomized either to receive 100 mg of CC on days 1-5 and placebo on days 5-9 (study group), or placebo on days 1-5 and CC on days 5-9 (control group). MAIN OUTCOME MEASURE(S): The difference in uterine artery PI, number of follicles, endometrial thickness, and pregnancy rates. RESULT(S): Gonadotropins and E2 levels, as well as uterine artery pulsatility index, were significantly higher in the study group on day 5. In addition, in the study group, a longer time interval existed between finishing CC and IUI (8 versus 6 days; MD = 2 days; 95% CI = 1-3) and the pregnancy rate was higher than in the control group (6 versus 0; OR = 15.1; 95% CI = 1.1-72.4). CONCLUSION(S): Clomiphene citrate commenced on day 1 of the menstrual cycle, rather than day 5, results in more rapid follicular growth, a longer CC-free period before IUI, and higher pregnancy rates. Although methodologically sound, our results should be taken with some degree of caution because they are based on a relatively small number of patients.
To investigate the effects of letrozole in patients undergoing superovulation with gonadotropins and IUI. Retrospective analysis. Academic teaching hospital. PATIENT(S): Women younger than 40 years of age with patent fallopian tubes and infertility of more than 1 year in duration who were undergoing IUI and gonadotropin therapy. INTERVENTION(S): Gonadotropins alone administered from day 3 or a combination of letrozole, 5 mg/d on day 3 to 7, and gonadotropins starting on day 5 of the menstrual cycle. Ultrasonography was performed before initiation of treatment, on day 9 of menstrual cycle, and as required thereafter until the dominant follicle reached 18 mm in diameter. Ovulation was triggered with 10,000 IU of hCG, and IUI was performed 24 and 48 hours later. MAIN OUTCOME MEASURE(S): Gonadotropin requirements, endometrial thickness, number of follicles, and pregnancy rate. RESULT(S): All 205 IUI treatment cycles conducted from March 2001 to March 2002 were included. Gonadotropins alone were used in 145 cycles and combination therapy was used in 60 cycles. Patients cotreated with letrozole required fewer gonadotropin administrations (median difference, 300 IU [95% confidence interval (CI), 225-375 IU]), developed more follicles larger than 14 mm (median difference, 1 follicle [95% CI, 1-2 follicles), and had a thinner endometrium (median difference, 1 mm [95% CI, 0.4-1.6 mm]). The pregnancy rate did not differ between patients using gonadotropin alone and those using gonadotropin plus letrozole (20.9% vs. 21.6%). CONCLUSION(S): The addition of letrozole to gonadotropins decreases gonadotropin requirements, increases the number of pre-ovulatory follicles and decreases endometrial thickness, without a negative effect on pregnancy rates.
PMID 14667861 14667861 DOI 10.1016/j.fertnstert.2003.05.002 10.1016/j.fertnstert.2003.05.002 Kilic-Okman et al. 2003, Kilic-Okman 2003
Cite this article
Kilic-Okman, T., Kucuk, M., & Altaner, S. (2003). Comparison of the effects of letrozole and clomiphene citrate on ovarian follicles, endometrium, and hormone levels in the rat. Fertility and sterility, 80(6), 1330-1332. https://doi.org/10.1016/j.fertnstert.2003.05.002
Kilic-Okman T, Kucuk M, Altaner S. Comparison of the effects of letrozole and clomiphene citrate on ovarian follicles, endometrium, and hormone levels in the rat. Fertil Steril. 2003;80(6):1330-1332. doi:10.1016/j.fertnstert.2003.05.002
Kilic-Okman, Tulay, et al. "Comparison of the effects of letrozole and clomiphene citrate on ovarian follicles, endometrium, and hormone levels in the rat." Fertility and sterility, vol. 80, no. 6, 2003, pp. 1330-1332.
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