Randomized Trial Comparing the Effect of Endometrial Shedding With Medroxyprogesterone Acetate With Random Start of Clomiphene Citrate for Ovulation Induction in Oligo-ovulatory and Anovulatory Women

Objective: A recent retrospective study demonstrated that anovulatory infertile women who did not have a progestogen-induced withdrawal bleed before treatment with clomiphene citrate (CC) had higher pregnancy rates than women who had a withdrawal bleed and those who had spontaneous menstrual bleeding. We sought to assess endometrial thickness at the time of ovulation in oligo-ovulatory and anovulatory women who took CC with or without a preceding progestogen-induced withdrawal bleed.

Methods: We conducted a pilot randomized trial in which women with infertility and oligomenorrhea or amenorrhea were randomly assigned to take either CC after a withdrawal bleed induced by medroxyprogesterone acetate (MPA) 10 mg daily for 10 days or to take CC without such a bleed. Study participants underwent cycle monitoring with ultrasound assessment of endometrial thickness at the time of LH surge or a human chorionic gonadotropin trigger, followed by timed intercourse or intrauterine insemination. Women who had not ovulated by cycle day 21 took an increased dose of CC, with or without an MPA-induced withdrawal bleed, to a maximum of three cycles. Participants and nurses were asked to complete a questionnaire about the study.

Results: There was no significant difference in endometrial thickness on the day of LH surge or human chorionic gonadotropin trigger between women who had a progestogen-induced withdrawal bleed and those who did not (P = 0.65). On average, the time to ovulation was 15 days longer in women who took MPA than in women who did not, but this difference was not statistically significant (P = 0.65). Satisfaction with the study was reported as high by both patients and nurses.

Conclusion: In anovulatory or oligo-ovulatory women treated with CC, we found no significant difference in endometrial thickness whether or not the use of CC was preceded by a withdrawal bleed induced by MPA.