A comparison of letrozole regimens for ovulation induction in women with polycystic ovary syndrome
Rachel S. Mandelbaum, M.D.,
Ravi Agarwal, M.D.,
Samuel Melville, M.D.,
Caroline J. Violette, M.D.,
Sharon Winer, M.D.,
Donna Shoupe, M.D.,
Koji Matsuo, M.D., Ph.D.,
Richard J. Paulson, M.D.,
Molly M. Quinn, M.D.
Affiliations
Rachel S. Mandelbaum, M.D.
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Southern California Keck School of Medicine, Los Angeles, California; Correspondence: Rachel S. Mandelbaum, M.D., Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Southern California, 2020 Zonal Avenue, IRD520, Los Angeles, CA 90033.
Ravi Agarwal, M.D.
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Southern California Keck School of Medicine, Los Angeles, California
Samuel Melville, M.D.
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Southern California Keck School of Medicine, Los Angeles, California
Caroline J. Violette, M.D.
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Southern California Keck School of Medicine, Los Angeles, California
Sharon Winer, M.D.
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Southern California Keck School of Medicine, Los Angeles, California
Donna Shoupe, M.D.
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Southern California Keck School of Medicine, Los Angeles, California
Koji Matsuo, M.D., Ph.D.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, California
Richard J. Paulson, M.D.
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Southern California Keck School of Medicine, Los Angeles, California
Molly M. Quinn, M.D.
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Southern California Keck School of Medicine, Los Angeles, California
Objective: To determine the optimal letrozole regimen for ovulation induction (OI) in women with polycystic ovary syndrome (PCOS) Design: Retrospective cohort study. Setting: Single academic fertility clinic from 2015–2022. Patient(s): A total of 189 OI cycles in 52 patients with PCOS Intervention(s): Patients were prescribed 1 of 4 letrozole regimens (group 1: 2.5 mg for 5 days, group 2: 2.5 mg for 10 days, group 3: 5 mg for 5 days, and group 4: 5 mg for 10 days). Main outcome measure(s): The primary outcome was ovulation, and secondary outcomes included multifollicular development, and clinical pregnancy rate, which were analyzed with binary logistic regression. Kaplan-Meier cumulative response curves and a Cox proportional hazard regression model were used for time-dependent analyses. Results: Mean age was 30.9 years (standard deviation [SD], 3.6) and body mass index was 32.1 kg/m2 (SD, 4.0). Group 2 (odds ratio [OR], 9.12; 95% confidence interval [CI], 1.92–43.25), group 3 (OR, 3.40; 95% CI, 1.57-7.37), and group 4 (OR, 5.94; 95% CI, 2.48–14.23) had improved ovulation rates after the starting regimen as compared with group 1. Cumulative ovulation rates exceeded 84% in all groups, yet those who received 5 mg and/or 10 days achieved ovulation significantly sooner. Multifollicular development was not increased in groups 2–4 as compared with group 1. Groups 2–4 also demonstrated improved time to pregnancy. Conclusions: Ovulation rates are improved when starting with letrozole at 5 mg and/or a 10-day extended course as compared with the frequently-used 2.5 mg for 5 days. This may shorten time to ovulation and pregnancy.
