Logo image
Back
RANDOMIZED CONTROLLED TRIAL OF COMBINED LETROZOLE AND CLOMIPHENE (CLC II) VERSUS LETROZOLE MONOTHERAPY FOR WOMEN WITH ANOVULATION
Abstract   Peer reviewed

RANDOMIZED CONTROLLED TRIAL OF COMBINED LETROZOLE AND CLOMIPHENE (CLC II) VERSUS LETROZOLE MONOTHERAPY FOR WOMEN WITH ANOVULATION

Rachel B. Mejia, Karen M. Summers, Jessica Kresowik, Laura G. Cooney, Abigail C. Mancuso, Emily A. Capper, Bala Bhagavath and Bradley J. Van Voorhis
Fertility and sterility, Vol.122(4 Supplement), pp.e75-e75
10/2024
DOI: 10.1016/j.fertnstert.2024.07.276

View Online

Abstract

OBJECTIVE To evaluate whether a combination of letrozole and clomiphene citrate results in higher ovulation rate than letrozole alone over three treatment cycles in women with infertility related to anovulation. MATERIALS AND METHODS Setting: Academic medical center utilizing four clinic sites. Patients: Women 18 to 40 years of age with infertility due to normogonadotropic normoestrogenic anovulation mainly secondary to polycystic ovary syndrome and no other cause of infertility. Interventions: Participants were randomized in a 1:1 ratio to either letrozole alone or combination of letrozole and CC, stratified by age, body mass index and clinic site. Women received either letrozole 2.5 mg or letrozole 2.5 and clomiphene citrate (CC) 50 mg daily on cycle days 3-7. The letrozole dose was increased if indicated in subsequent cycles in both groups based on ovulatory response and ultrasound findings. Dose was increased immediately if anovulatory and no follicular development. Participants completed up to three treatment cycles. Main Outcome Measures: Ovulation measured by mid-luteal progesterone level with a serum progesterone concentration of > 3 ng/mL to indicate ovulation. Sample size: The study was designed to have 80% power to detect a 20% absolute difference in ovulation rate between the two groups using Pearson’s chi-square test at a two-sided significance level of 0.05. RESULTS One-hundred and ninety participants were randomized, 98 to letrozole alone and 92 to combination letrozole and CC. Participants were analyzed within the treatment group they were assigned to at randomization and results were analyzed with the intent-to-treat principle. The combination of letrozole and CC had a higher ovulation rate (ovulations/treatment cycles) compared to the ovulation rate of letrozole alone (190/232 [81.9%] vs. 192/269 [71.4%], P=0.017; rate ratio for ovulation 1.81; 95% CI 1.11 – 2.96). The number of women that achieved ovulation at least once over three treatment cycles was not different between the two groups, 96.7% in the combination group and 92.9 % in letrozole group. There were no significant differences in clinical pregnancy rate, with 33.7% in the combination group and 27.6% in the letrozole group. There were two twin pregnancies in each group. CONCLUSIONS The combination of letrozole and CC was associated with a higher ovulation rate compared to letrozole alone, among women with infertility and PCOS or WHO group II anovulation. IMPACT STATEMENT The novel combination treatment of letrozole and CC resulted in a higher ovulation rate than letrozole alone and a trend towards increased pregnancy rate over 3 treatment cycles without an increase in multiple births. This treatment could be used as a first line or alternative treatment to help achieve ovulation in women with anovulatory infertility.

Details

Metrics

57 Record Views
Logo image