Evaluation of the relationship between plasma concentrations of en- and zuclomiphene and induction of ovulation in anovulatory women being treated with clomiphene citrate.
OBJECTIVE
To investigate the relationship between the plasma concentrations of clomiphene citrate (CC) isomers zu- (Zu) and enclomiphene (En), and ovulation outcome.


METHODS
Prospective, cohort study.


METHODS
Reproductive medicine and fertility center in a university teaching hospital, United Kingdom.


METHODS
Forty-two women with World Health Organization type 2 infertility.


METHODS
The clinical and biochemical features of patients who were about to start CC for induction of ovulation were recorded. Plasma concentration of Zu and En were monitored at three points (days 2, 8, and 21) throughout the treatment cycle(s).


METHODS
Ovulation.


RESULTS
Thirty-nine patients completed the study. Both En and Zu accumulated throughout treatment. Among the 36 responders, there was no statistically significant relationship between the clinical and biochemical characteristics of the patients, En or Zu concentrations, and the dose required to induce ovulation. Moreover, the Zu and En concentrations were not different in the three patients who failed to respond.


CONCLUSIONS
The concentrations of En and Zu in plasma, on their own or in combination with other covariates (e.g., weight, body mass index, free androgen index), are not a predictor of the ovulation response to CC or of the dose requirement. Further studies are needed to explore the role of additional covariates, including the presence of active metabolites, and the balance of the effects of En and Zu.
Ghobadi
Cyrus
C
Academic Unit of Clinical Pharmacology, University of Sheffield, Sheffield, United Kingdom.
Amer
Saad
S
Lashen
Hany
H
Lennard
Martin S
MS
Ledger
William L
WL
Rostami-Hodjegan
Amin
A
D000328:Adult; D000858:Anovulation / Q000097:blood* / Q000188:drug therapy*; D015992:Body Mass Index; D002996:Clomiphene / Q000097:blood* / Q000627:therapeutic use*; D064695:Enclomiphene; D005260:Female; D005300:Fertility Agents, Female / Q000097:blood / Q000627:therapeutic use; D006801:Humans; D010060:Ovulation / Q000187:drug effects; D010062:Ovulation Induction / Q000379:methods*; D012372:ROC Curve; D013997:Time Factors; D055815:Young Adult
D005300:Fertility Agents, Female; D002996:Clomiphene; D064695:Enclomiphene