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.

Design

Prospective, cohort study.

Setting

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

Patient(s)

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

Intervention(s)

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).

Main Outcome Measure(s)

Ovulation.

Result(s)

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.

Conclusion

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.

Key Words: Clomiphene citrate, concentration–response, clomiphene isomers, ovulatory response, infertility treatment, normogonadotropic anovulatory infertility