Letrozole versus Clomiphene Citrate for Induction of Ovulation in Patients with Polycystic Ovarian Syndrome Undergoing Intrauterine Insemination

Abstract

BackgroundPolycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting women in the reproductive age group, and is one of the most common causes of hyperandrogenic anovulatory infertility. The aromatase inhibitor, letrozole, has been used for induction of ovulation. The purpose of this study was to compare the effects of letrozole and clomiphene citrate in induction of ovulation among patients with PCOS undergoing intrauterine insemination.MethodsIn a double-blind randomized study, 60 infertile patients with PCOS received standard doses of either clomiphene citrate or letrozole as an induction protocol prior to intrauterine insemination. A hormonal profile, pelvic ultrasound, hysterosalpingogram, and/ or laparoscopy were done for all patients. The patients were monitored for ovulation by translational ultrasonographic folliculometry, with measurement of number and size of the follicles, as well as endometrial thickness. Human chorionic gonadotrophin (HCG) was injected intramuscularly when at least one mature follicle ≥18 mm diameter was detected, and intrauterine insemination was performed 32–36 hours later. Transvaginal ultrasound and β-HCG measurement were performed for confirmation of pregnancy.ResultsLetrozole and clomiphene citrate achieved follicle maturation within a mean ± standard deviation (SD) of 13.2 ± 1.53 and 14.1 ± 1.35 days, respectively, showing no significant difference (P > 0.05). The mean number of follicles reaching ≥18 mm on the day of HCG administration was significantly higher in patients who received clomiphene citrate (2.9 ± 1.77) than in those receiving letrozole (1.2 ± 0.9). Letrozole had a significantly greater effect than clomiphene citrate on endometrial thickness (9.16 ± 1.36 versus 4.46 ± 1.71). The number of pregnancies achieved in the letrozole group was significantly (P < 0.05) greater than in the clomiphene group.ConclusionLetrozole in patients with PCOS is as effective as clomiphene citrate in inducing ovulation, and although the number of follicles produced by induction with letrozole were less than those produced by clomiphene, letrozole had a significantly greater effect on endometrial thickness than clomiphene citrate, and the incidence of pregnancy after intrauterine insemination was significantly higher, with a lower incidence of multiple pregnancy.

Effect of clomiphene citrate on endometrial thickness, ovulation, pregnancy and live birth in anovulatory women: systematic review and meta‐analysis

“…In the three studies with low risk of allocation concealment bias, the comparison between CC and letrozole showed lower EMT in the CC group (WMD, −1.68; 95% CI, −3.27 to −0.08; I 2 = 98%). However, including studies with low risk of randomization bias, performance bias and detection bias showed a similar effect estimate but without statistical significance, which could be due to low power of the studies.…”

“…Pooled analysis of 15 studies showed EMT to be lower (WMD, −1.39; 95% CI, −2.27 to −0.51; I 2 = 100%) with a lower pregnancy rate (RR, 0.78; 95% CI, 0.63–0.95; I 2 = 43%) in the CC group than in the letrozole group (Figures and ). Ovulation rates were comparable between the groups (13 trials, RR, 0.97; 95% CI, 0.90–1.04; I 2 = 47%; Figure ). Data of EMT per woman were available in eight studies; pooled analysis showed EMT to be lower in the CC group (WMD, −2.10; 95% CI, −3.22 to −0.98; I 2 = 96%).…”

“…There were 33 RCTs comprising a total of 4349 women with WHO group II anovulation, undergoing 7210 treatment cycles. Of the 33 included studies, participants were women with PCOS (without CC resistance) in 25 studies, women with CC‐resistant PCOS in five studies, women with WHO group II anovulation (with or without PCOS) in two studies and women with WHO group II anovulation (without PCOS) in one study. The characteristics of these 33 included studies are listed in Table .…”

“…Risk of bias for included studies is presented in a summary table ( Figure S1). We included 15 RCTs comparing CC with letrozole (1957 women, 3892 cycles) [23][24][25][27][28][29]33,[38][39][40][41]44,46,51,54 , two RCTs comparing CC with anastrozole (329 women, 329 cycles) 52,53 , two RCTs comparing CC with CC plus metformin (101 women, 140 cycles) 35,42 , three RCTs comparing CC with tamoxifen (571 women, 844 cycles) 26,38,54 , three RCTs comparing CC with CC plus N-acetyl cysteine (NAC; 340 women, 300 cycles) 35,43,49 and two RCTs comparing CC with CC plus isosorbide mononitrate (ISMN) as nitric oxide (NO) donor (120 women, 304 cycles) 30,36 .…”

“…Pooled analysis of five studies showed a lower live birth rate in the CC group (RR, 0.70; 95% CI, 0.49-0.98; I 2 = 35%) 27,29,40,41,54 (Figure 2). Pooled analysis of 15 studies showed EMT to be lower (WMD, −1.39; 95% CI, −2.27 to −0.51; I 2 = 100%) with a lower pregnancy rate (RR, 0.78; 95% CI, 0.63-0.95; I 2 = 43%) in the CC group than in the letrozole group (Figures 2 and 3) [23][24][25][27][28][29]33,[38][39][40][41]44,46,51,54 .…”