Alexandra P Tsiami1, Dimitrios G Goulis2, Alexandros I Sotiriadis3, Efstratios M Kolibianakis4. 1. National and Kapodistrian University of Athens, Irakleitou 1, 50132, Kozani, Greece. alexandratsiami@hotmail.gr. 2. Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Papageorgiou General Hospital, Aristotle University of Thessaloniki, 54629, Thessaloniki, Greece. 3. 2nd Department of Obstetrics and Gynecology, Faculty of Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, 54642, Thessaloniki, Greece. 4. Unit of Human Reproduction, 1st Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki Papageorgiou General Hospital, 54629, Thessaloniki, Greece.
Abstract
BACKGROUND: Polycystic ovary syndrome (PCOS) is a common cause of anovulatory infertility. According to the latest guidelines, letrozole should be considered as the first-line pharmacological treatment for women with WHO Group II anovulation or PCOS. However, the use of letrozole as an ovulation induction agent is not FDA or EMA approved, and its use is "off-label." The main concern with respect to letrozole regards its potential teratogenic effect on the fetus. PURPOSE: To determine whether the probability of ovulation is higher with letrozole as compared to clomiphene citrate (CC) in anovulatory women with PCOS. METHODS: Randomized controlled trials (RCTs) comparing letrozole versus CC used for ovulation induction in infertile women with PCOS followed by timed intercourse (TI) or intrauterine insemination (IUI) were included in this meta-analysis. Primary outcome was ovulation. Secondary outcomes were live birth, clinical pregnancy, miscarriage, multiple pregnancy, and congenital anomalies. Subgroup analysis included patients who received letrozole or CC as first-line treatment, and patients with PCOS diagnosed according to the Rotterdam criteria. RESULTS: Twenty-six RCTs published between 2006 and 2019, involving 4168 patients who underwent 8310 cycles of ovulation induction, were included. The probability of ovulation was significantly higher in letrozole as compared to CC cycles (RR: 1.148, 95% CI: 1.077 to 1.223, 3017 women, 19 trials, I2: 47.7%, low-quality evidence). CONCLUSION: A higher probability of ovulation is expected in infertile patients with PCOS treated with letrozole as compared to CC. The higher ovulation rate might have contributed to the higher clinical pregnancy and live birth rate. This finding is also true for patients who were administered letrozole as first-line treatment. TRIAL REGISTRATION: CRD42019125166.
BACKGROUND: Polycystic ovary syndrome (PCOS) is a common cause of anovulatory infertility. According to the latest guidelines, letrozole should be considered as the first-line pharmacological treatment for women with WHO Group II anovulation or PCOS. However, the use of letrozole as an ovulation induction agent is not FDA or EMA approved, and its use is "off-label." The main concern with respect to letrozole regards its potential teratogenic effect on the fetus. PURPOSE: To determine whether the probability of ovulation is higher with letrozole as compared to clomiphene citrate (CC) in anovulatory women with PCOS. METHODS: Randomized controlled trials (RCTs) comparing letrozole versus CC used for ovulation induction in infertile women with PCOS followed by timed intercourse (TI) or intrauterine insemination (IUI) were included in this meta-analysis. Primary outcome was ovulation. Secondary outcomes were live birth, clinical pregnancy, miscarriage, multiple pregnancy, and congenital anomalies. Subgroup analysis included patients who received letrozole or CC as first-line treatment, and patients with PCOS diagnosed according to the Rotterdam criteria. RESULTS: Twenty-six RCTs published between 2006 and 2019, involving 4168 patients who underwent 8310 cycles of ovulation induction, were included. The probability of ovulation was significantly higher in letrozole as compared to CC cycles (RR: 1.148, 95% CI: 1.077 to 1.223, 3017 women, 19 trials, I2: 47.7%, low-quality evidence). CONCLUSION: A higher probability of ovulation is expected in infertile patients with PCOS treated with letrozole as compared to CC. The higher ovulation rate might have contributed to the higher clinical pregnancy and live birth rate. This finding is also true for patients who were administered letrozole as first-line treatment. TRIAL REGISTRATION: CRD42019125166.
Authors: Adam H Balen; Lara C Morley; Marie Misso; Stephen Franks; Richard S Legro; Chandrika N Wijeyaratne; Elisabet Stener-Victorin; Bart C J M Fauser; Robert J Norman; Helena Teede Journal: Hum Reprod Update Date: 2016-08-10 Impact factor: 15.610
Authors: Richard S Legro; Silva A Arslanian; David A Ehrmann; Kathleen M Hoeger; M Hassan Murad; Renato Pasquali; Corrine K Welt Journal: J Clin Endocrinol Metab Date: 2013-10-22 Impact factor: 5.958