Letrozole or Clomiphene Citrate for Induction of Ovulation in Patients with Polycystic Ovarian Syndrome: A Prospective Randomized Trial

Abstract

Polycystic Ovarian Syndrome (PCOS) is the most common endocrine disorder responsible for subfertility in young women. The aim of the study was to compare the efficacy of Letrozole over Clomiphene citrate (CC) for ovulation induction in patients with PCOS. It was a prospective randomized trial in a private practice setting. The study period was 3 years, which includes 240 sub fertile patients with PCOS. Patients were divided into two groups. Group-A: 120 patients got Letrozole (2.5 mg) tab, 2 tabs once daily from D 2 -D 6 for 3 cycles. Group-B: 120 patients took tab. Clomiphene citrate (50mg), 2 tabs once daily from D 2 -D 6 for 3 cycles. Trans-vaginal ultrasound was done on D 12 -D 13 to document number of follicles, measurement of dominant follicle and endometrial thickness. Ovulation and pregnancy rate was measured. Results showed that Letrozole have significantly better effect on endometrial thickness (Let 9.2 mm vs CC 8.1 mm) and pregnancy rate (Let 44% vs CC 24%). In CC, multiple follicles were found (CC 44% vs Let 30%). Ovulation occurred in 65% with Letrozole group and 64% in CC group without a significant statistical difference. The study concluded that Letrozole have better effect for induction of ovulation in PCOS patient in comparison to CC.

Effect of Body Mass Index on Ovulation in Nigerian Women With Polycystic Ovarian Syndrome Undergoing Treatment With Clomiphene Citrate: A Sonographic Study.

“…In this study, women with PCOS had significantly higher BMI than their healthy counterpart (control group). This finding is in harmony with the findings of the studies carried out by Dumesic et al [6], Al-Shattawi et al [15] and Doh et al [16] ,which also reported high BMI among subjects with PCOS. According to Doh et al [16], they hypothesized that PCOS and obesity act synergistically and independently resulting in insulin resistance (IR).…”

“…This finding is in harmony with the findings of the studies carried out by Dumesic et al [6], Al-Shattawi et al [15] and Doh et al [16] ,which also reported high BMI among subjects with PCOS. According to Doh et al [16], they hypothesized that PCOS and obesity act synergistically and independently resulting in insulin resistance (IR). In Dumesic et al [6] study, they noted that dual-energy X-ray absorptiometry have revealed increased accumulation of central fat in women with PCOS.…”

Efficacy of Letrozole vs Clomiphene Citrate for induction of ovulation in women with polycystic ovarian syndrome

“…In our study, the ovulation rate was not statistically significantly different between the two study groups (CC 63.6%, Letrozole 68.1%, p= 0.47) which is similar to the studies by Zeba D et al and Liu C et al 14 , 15 While Amer SA et al, Khakwani M et al, Najafi PZ et al and Sakar et al reported significantly better ovulation in letrozole group. 6 , 10 , 16 , 17 One of the issues with ovulation induction drugs is chances of multiple follicular development and hyperstimulation.…”

“…Following this, other RCTs were reported supporting letrozole being better in achieving pregnancy and live birth. 5 , 6 , 14 - 16 Liu C et al and Saha J et al recommend no significant difference in ovulation and pregnancy rate in RCT with both drugs and recommend clomiphene citrate as first line drugs 15 , 18 . Wang R et al and Roque M et al in meta-analysis comprising of 1284 and 3962 patients have demonstrated that Letrozole use resulted in significantly better clinical pregnancy and live birth rate compared to clomiphene citrate in women with PCOS.…”

“…Treatment with Clomiphene has been reported to be associated with 10-12% chances of having twins compared to 3-5% with letrozole. 5 , 14 Aromatase inhibitors are selective estrogen receptor modulator, do more physiological hormonal stimulation of endometrium, lower multiple pregnancy rate due to single follicular recruitment. Letrozole showed highly statistically significant monofollicular development (77.2% vs 52.7% p-value 0.000) in our study.…”