Comparison of the efficacy of letrozole and low-dose gonadotropin combination with clomiphene and low-dose gonadotropin combination as a controlled ovarian stimulation regime prior to intrauterine insemination in patients with unexplained infertility

Abstract

Objective: To evaluate and compare the effects of letrozole and low-dose gonadotropin combination with clomiphene citrate (CC) and low-dose gonadotropin combination prior to intrauterine insemination (IUI) in patients with unexplained infertility. Design: Prospective, randomized, clinical study. Setting: Academic tertiary institute. Patient(s): A total of 94 patients in the age group of 21-37 years with unexplained infertility were randomized using computer-generated random number table to receive follicle-stimulating hormone (FSH) injection and human menopausal gonadotropin (hMG) injection, along with either letrozole or CC. Intervention(s): All the patients received 150 IU of purified urinary FSH on day 2 of the cycle and from day 3 to day 7 of the cycle 5.0 mg/d of letrozole or 100 mg/d of CC were administered; this was followed by administration of 150 IU of hMG on day 9. Ovulation was triggered with human chorionic gonadotropin (hCG) injection (5,000 IU) when the dominant follicle(s) reached 18 mm in diameter. A single IUI was performed 36 h later. The luteal phase was supplemented with micronized progesterone vaginally. Main Outcome Measure(s): Pregnancy rates and the incidence of multiple pregnancies were our primary outcome. The secondary outcome included the number of dominant follicles, grade of perifollicular blood flow, endometrial thickness, endometrial blood flow pattern, side effects, and complications. Result(s): There were no differences in demographic characteristics between the two groups. Pregnancy occurred in four out of 47 patients (120 cycles) in the letrozole group (pregnancy rate: 8.5% per patient and 3.3% per cycle) and eight out of 47 patients (121 cycles) (pregnancy rate: 17% per patient and 6.6% per cycle) in the CC group; the differences were not statistically significant. None of the regimes resulted in a multiple gestation gestation. The number of follicles per cycle was significantly higher in the CC + gonadotropin group as compared to the letrozole + gonadotropin group (1.77 ± 0.99 vs. 1.39 ± 0.617, P < 0.001). There was no statistically significant difference in perifollicular blood flow, endometrial thickness, and endometrial blood flow pattern between the two groups. No side effects were observed in either group. There was one case of ectopic gestation in the CC group. Conclusion(s): The use of lower dose of gonadotropins and oral agents together resulted in decreased medication costs, lesser monitoring [ultrasound (USG) visits], and good primary and secondary outcomes. However, more randomized controlled trials are needed to prove the efficacy of one regime over the other.