Daly, D. C., Walters, C. A., Soto-Albors, C. E., Tohan, N., & Riddick, D. H. (1984). A randomized study of dexamethasone in ovulation induction with clomiphene citrate. Fertility and Sterility, 41(6), 844-848. https://doi.org/10.1016/s0015-0282(16)47896-9
Daly DC, Walters CA, Soto-Albors CE, Tohan N, Riddick DH. A randomized study of dexamethasone in ovulation induction with clomiphene citrate. Fertil Steril. 1984;41(6):844-848. doi:10.1016/s0015-0282(16)47896-9
Daly, Douglas C., et al. "A randomized study of dexamethasone in ovulation induction with clomiphene citrate." Fertility and Sterility, vol. 41, no. 6, 1984, pp. 844-848.
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University of Connecticut Health Center, Farmington.
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RRM Academy Synopsis
Dexamethasone plus clomiphene raised ovulation in a small trial
A small 1984 randomized trial of 64 women who did not ovulate found that dexamethasone added to clomiphene raised ovulation and pregnancy. The gain appeared mainly in women with higher adrenal androgen levels. All 23 women on both drugs ovulated, against 14 of 22 on clomiphene alone.
Key Findings
Sixty-four women were randomized, 32 to each arm. After 9 early dropouts and 10 women with another cause of infertility, 22 took clomiphene alone and 23 took clomiphene plus dexamethasone.
All 23 women on clomiphene plus dexamethasone ovulated. Only 14 of 22 on clomiphene alone did (P < 0.01).
Seventeen of 23 women on the combination conceived viable pregnancies, 3 of them twins. Eight of 22 on clomiphene alone did (P < 0.05).
In women with higher DHEA-S, 13 of 13 on the combination ovulated against 6 of 12 on clomiphene alone. Conception was 11 of 13 against 4 of 12.
In women with lower DHEA-S, ovulation was 10 of 10 against 8 of 10, and conception 6 of 10 against 4 of 10. Neither difference was statistically significant.
Interpretation
This is a small randomized trial from one university center, so the subgroup results rest on groups of 10 to 13 women. The authors judge that the higher ovulation rate is the major cause of the higher pregnancy rate. Once women ovulated, conception rates did not differ significantly between arms. The trial reports viable pregnancies and no live birth counts. The women had no ovulation on charting or irregular periods, had not taken clomiphene before, and were screened for other causes before analysis.
RRM Context
Ten of the 64 women left the trial after screening found high prolactin, severe male factor, or tubal disease. Restorative reproductive medicine looks for the cause of missed ovulation in each woman. This trial shows why that workup comes first. Basal body temperature charting helped identify who was not ovulating.
Our editorial summary of this paper, not the article's abstract.
Abstract
Improved understanding of follicular dynamics has led to a reevaluation of suppression of adrenal androgens in ovulation induction. To test whether adrenal suppression during clomiphene citrate (CC) therapy would improve ovulation/pregnancy rates, 64 anovulatory patients who had not previously received CC were randomly assigned to receive either 50 mg CC on days 5 to 9 alone or with 0.5 mg dexamethasone (CC + DEX). Patients were then screened for dehydroepiandrosterone sulfate (DHEA-S) (normal range, 80 to 320 micrograms/dl), prolactin, testosterone, and semen analysis of the partner. Nine patients discontinued participation prior to completing the first treatment cycle, and ten patients were found to have either elevated prolactin (4), severe male factors (3), or tubal disease (3) and were discontinued. CC was increased 50 mg/day per cycle through 150 mg/day until ovulation occurred. Once the patient was ovulatory on therapy, a properly timed postcoital test and endometrial biopsy for luteal phase defect were performed. If anovulatory at 150 mg/day of CC or demonstrating abnormal postcoital test or endometrial biopsy at 150 mg/day of CC, patients were crossed to the other arm of the treatment protocol. The results revealed a significantly higher rate of ovulation (P less than 0.01) and conception (P less than 0.05) in the CC + DEX-treated group. When correlated with DHEA-S levels, this improvement occurred in patients with DHEA-S greater than 200 micrograms/dl (P less than 0.05).
