Isaacs, J. D., Jr., Lincoln, S. R., & Cowan, B. D. (1997). Extended clomiphene citrate (CC) and prednisone for the treatment of chronic anovulation resistant to CC alone. Fertility and Sterility, 67(4), 641-643. https://doi.org/10.1016/s0015-0282(97)81359-3
Isaacs JD Jr, Lincoln SR, Cowan BD. Extended clomiphene citrate (CC) and prednisone for the treatment of chronic anovulation resistant to CC alone. Fertil Steril. 1997;67(4):641-643. doi:10.1016/s0015-0282(97)81359-3
Isaacs, John D., Jr., et al. "Extended clomiphene citrate (CC) and prednisone for the treatment of chronic anovulation resistant to CC alone." Fertility and Sterility, vol. 67, no. 4, 1997, pp. 641-643.
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Most clomiphene-resistant women ovulated on clomiphene plus prednisone
11 of 24 women resistant to clomiphene conceived on extended clomiphene plus prednisone. Resistance meant no ovulation on a usual five-day course. A university clinic looked back at their charts. The 60 treatment cycles had no comparison group. Of these, 44 were ovulatory.
Key Findings
Eleven of 24 women (46%) conceived on extended clomiphene plus prednisone. Two of the pregnancies ended in spontaneous abortion, and one was a twin gestation.
Nineteen of 24 women (79%) became ovulatory, and 44 of 60 treatment cycles (73%) resulted in ovulation.
Logistic analysis gave a cycle fecundity (the chance of pregnancy in each cycle) of 0.36. The maximum cumulative probability of conception reached 0.66.
The 24 women completed 60 cycles, a mean of 2.5 per woman (range 1 to 8). Record review found no side effects related to clomiphene or prednisone.
Interpretation
The report looks back at the charts of 24 women at one university clinic. It has no comparison group. The authors name three limits: possible selection bias, a sample too small for reliable estimates, and no test of extended clomiphene without prednisone. The women had a normal tube X-ray or diagnostic laparoscopy, normal thyroid and prolactin levels, and a normal semen analysis in the male partner. Earlier, they had averaged 7 cycles of escalating clomiphene.
RRM Context
In their discussion, the authors suggest that glucocorticoids may lower adrenal androgens and may change GnRH pulsing. Serum androgen levels were not consistently available. The study did not examine mechanism. Restorative reproductive medicine asks why ovulation fails before choosing a drug. This series leaves that question open for its adrenal androgen idea.
Our editorial summary of this paper, not the article's abstract.
Abstract
Objective
To evaluate effectiveness and safety of a regimen of extended clomiphene citrate (CC) and prednisone for patients who fail treatment with CC alone.
Design
Retrospective observational analysis.
Setting
University-based tertiary infertility center.
Patients
Twenty-four anovulatory patients who failed to ovulate after CC 150 mg administered for 5 days.
Interventions
Treatment consisted of CC given on cycle days 3 through 9 (extended) at a starting dose of 100 to 150 mg/d. Additionally, patients were given prednisone 5 mg orally each night throughout the cycle.
Main Outcome Measures
Ovulation was confirmed by luteal serum P. Pregnancy was confirmed by rising hCG levels and transvaginal ultrasound.
Results
A total of 60 cycles were available for review. Forty-four of these cycles were ovulatory (73%) and 11 patients (46%) conceived on this therapy. Logistic (two-parameter) pregnancy occurrence over time (cycles) revealed a maximum pregnancy probability of 0.66 and a cycle fecundity of 0.36. No complications of therapy were noted.
Conclusions
Clomiphene citrate-resistant anovulatory patients have high rates of ovulation and pregnancy after treatment with extended CC and prednisone. This therapy offers a potential reduction in cost and risk and should be considered in this group of patients before gonadotropin stimulation or surgery.
