Effect of letrozole on uterine artery Doppler flow indices prior to first-trimester termination of pregnancy: a randomized controlled trial.
OBJECTIVE
We previously demonstrated that a sequential regimen of letrozole and misoprostol resulted in a marked reduction in the serum estradiol concentration and in a higher efficacy of first-trimester termination of pregnancy than misoprostol alone. The aim of this study was to evaluate the effect of letrozole on uterine artery Doppler flow indices during early pregnancy.


METHODS
This was a randomized controlled trial. Thirty women requesting termination of pregnancy up to 63 days' gestation were randomized into two groups: a letrozole group receiving 10 mg of letrozole, daily, for 3 days, and a control group receiving a placebo for 3 days. Serum estradiol, progesterone and human chorionic gonadotropin (hCG) concentrations were measured before drug administration and then daily for 6 days. Ultrasound scanning for fetal viability and measurement of the pulsatility (PI) and resistance (RI) indices of the uterine arteries was performed before drug administration, and then on day 3 and day 7 after starting letrozole or placebo. All pregnancies were terminated by surgical evacuation on day 7 or day 8.


RESULTS
Uterine artery PI and RI decreased significantly in the letrozole group, but not in the control group. Serum estradiol concentrations were significantly lower in the letrozole group than in the control group from day 2 onwards. Serum progesterone and hCG concentrations were comparable for the two groups throughout the 7 days. There were significantly more women in the letrozole group with vaginal bleeding.


CONCLUSIONS
We have demonstrated that the use of letrozole in the first trimester of pregnancy suppresses serum estradiol levels but results in an increase in blood flow to the uterus. Further studies should be carried out to elucidate the mechanism of letrozole pretreatment in medical abortion.
Department of Obstetrics & Gynecology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China. v200lee@hku.hk
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D000020:Abortifacient Agents, Nonsteroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000028:Abortion, Induced / Q000379:methods*; D000328:Adult; D006063:Chorionic Gonadotropin / Q000097:blood; D004958:Estradiol / Q000097:blood; D005260:Female; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage / Q000494:pharmacology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011300:Preoperative Care; D011374:Progesterone / Q000097:blood; D011673:Pulsatile Flow / Q000187:drug effects*; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology*; D018608:Ultrasonography, Doppler; D055988:Uterine Artery / Q000000981:diagnostic imaging* / Q000187:drug effects* / Q000503:physiopathology; D014592:Uterine Hemorrhage / Q000139:chemically induced*
D000020:Abortifacient Agents, Nonsteroidal; D006063:Chorionic Gonadotropin; D009570:Nitriles; D014230:Triazoles; D011374:Progesterone; D004958:Estradiol; D000077289:Letrozole