How to Choose the Optimal Starting Dose of Clomiphene Citrate (50 or 100 mg per Day) for a First Cycle of Ovulation Induction in Anovulatory PCOS Women?

RESEARCH QUESTION

Clomiphene citrate (CC) is one of the first-line treatments for ovulation induction in women with anovulatory polycystic ovary syndrome (PCOS). However, nearly 1 out of 2 women is resistant to 50 mg/day of CC. The objective of this study is to investigate the clinical, biological, and/or ultrasound factors that may predict the resistance to 50 mg/day of CC in the first cycle of treatment in women with anovulatory PCOS. This would make it possible to identify PCOS patients to whom the dose of 100 mg/day would be offered as of the first cycle.

DESIGN

A retrospective and monocentric study was conducted on 283 women with anovulatory PCOS who required the use of ovulation induction with CC (903 cycles).

RESULTS

During the first cycle of treatment, 104 patients (36.8%) were resistant to 50 mg/day of CC. Univariate regression analysis showed that patients who resisted 50 mg/day of CC had significantly higher BMI, waist circumference, serum levels of AMH, total testosterone, Δ4-androstenedione, 17-OHP, and insulin ( < 0.05), compared to patients ovulating with this dose. Serum levels of SHBG were significantly lower in patients resistant to 50 mg/day ( < 0.05). After multivariate analysis, only AMH and SHBG remained statistically significant ( = 0.01 and = 0.001, respectively). However, areas under the ROC curves were weak (0.59 and 0.68, respectively).

CONCLUSION

AMH and SHBG are the only two parameters significantly associated with the risk of resistance to 50 mg/day of CC. However, no satisfactory thresholds have been established to predict resistance to 50 mg CC.