Clomiphene failure? Try adding dexamethasone to your clomiphene infertility regimen
Clomiphene-resistant women often ovulate, and then become pregnant, when treated with a combination of clomiphene and dexamethasone
Plotting a cycle of clomiphene plus dexamethasone, and accompanying testing
STEP 3 Measure serum progesterone approximately 7 to 10 days after the LH surge
Evidence of successful ovulation is an appropriately drawn serum progesterone level >8 ng/mL; in most clomiphene cycles in which successful ovulation has occurred, the serum progesterone level is >20 ng/mL.
If menses does not occur within 17 days after the LH surge, obtain a pregnancy test. If the combination of clomiphene, 100 mg/d for 5 days, plus dexamethasone does not cause ovulation, prescribe a cycle of clomiphene, 150 mg/d for cycle Days 3 to 7, plus dexamethasone.
If that regimen does not cause ovulation, advise the patient to consider other options for ovulation induction—such as weight loss, FSH injection, laparoscopic ovarian drilling, and IVF.
Caution on the duration of therapy. Experts recommend that clomiphene therapy for infertility be limited to no more than approximately 6 to 12 cycles; the concerns are that prolonged clomiphene treatment may increase the risk of ovarian neoplasm8 and that the pregnancy rate per cycle may decrease with prolonged use of clomiphene.
Women who use clomiphene should also be aware that approximately 8% of clomiphene-induced pregnancies are twin gestations and <0.5% are triplet gestations.
CASE Resolved, on labor and delivery
The clomiphene-resistant woman described at the beginning of the Editorial underwent HSG that showed bilaterally patent tubes, of normal caliber. Her partner’s semen analysis was normal.
She was treated with clomiphene plus dexamethasone, and ovulated. She became pregnant, and delivered a singleton newborn, at term.
Consider estrogen-progestin for 2 months, leading up to a clomiphene cycle
Another treatment option that can enhance the efficacy of clomiphene in women who are resistant to the drug is to prescribe 2 months of an estrogen–progestin contraceptive, then stop the contraceptive and prescribe a standard cycle of clomiphene. A randomized trial has demonstrated the effectiveness of this regimen for clomiphene-resistant patients.1
In the report of the trial by Branigan and Estes,1 women who failed to ovulate with clomiphene, 150 mg/d for 5 days, were randomized to:
- 42 to 50 days of ethinyl estradiol, 0.03 mg, plus desogestrel (Desogen), 0.15 mg, before a clomiphene cycle (Group 1) or
- no treatment before a clomiphene cycle (Group 2, controls).
After a withdrawal bleed (Group 1) or spontaneous menses (Group 2), all subjects were treated with clomiphene, 100 mg/d, for cycle Days 5 to 9. Women in Group 1 exhibited a 55% mean decrease in serum testosterone (P <.001); women in the control group had a 6% mean decrease in serum testosterone (no significant change). Across six treatment cycles, the pregnancy rate was 54% (Group 1) and 4% (Group 2) (P <.001).
The researchers’ conclusion? Lowering serum testosterone with estrogen–progestin pretreatment might improve responsiveness to clomiphene-induced ovulation.
Reference
A woman seeing pregnancy has PCOS and anovulatory infertility, and is clomiphene-resistant. What is your preferred next step in management?
