Prospective randomized double-blind trial of the correlation between time of administration and antiestrogenic effects of clomiphene citrate on reproductive end organs.
OBJECTIVE
To investigate whether the timing of administration of clomiphene citrate (CC) affects hormone levels, follicular recruitment, reproductive end organs, and pregnancy rates.


METHODS
Prospective, randomized, double-blind trial.


METHODS
Academic center.


METHODS
Twenty-three patients with unexplained infertility.


METHODS
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).


METHODS
The difference in uterine artery PI, number of follicles, endometrial thickness, and pregnancy rates.


RESULTS
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).


CONCLUSIONS
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.
Biljan
M M
MM
McGill Reproductive Center, Department of Obstetrics and Gynecology, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada. mbiljan@rvhob2.lan.mcgill
Mahutte
N G
NG
Tulandi
T
T
Tan
S L
SL
D000328:Adult; D002996:Clomiphene / Q000008:administration & dosage*; D004311:Double-Blind Method; D004958:Estradiol / Q000097:blood; D004965:Estrogen Antagonists / Q000008:administration & dosage*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007246:Infertility / Q000628:therapy*; D007315:Insemination, Artificial; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D006080:Ovarian Follicle / Q000000981:diagnostic imaging; D010062:Ovulation Induction; D010919:Placebos; D011247:Pregnancy; D011446:Prospective Studies; D011673:Pulsatile Flow; D014463:Ultrasonography; D014599:Uterus / Q000098:blood supply
D004965:Estrogen Antagonists; D010919:Placebos; D002996:Clomiphene; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone