COST EFFECTIVE PROTOCOL WITH LETROZOLE AND 3 DOSES OF GONADOTROPIN COMBINATION AS AN ALTERNATIVE TO CONTINUOUS GONADOTROPIN FOR OVULATION INDUCTION FOR IUI IN CLOMIPHENE CITRATE RESISTANT PCOS PATIENTS - A RCT

Abstract

Clomiphene citrate (CC) is the primary drug of choice for ovulation induction in PCOS but resistance to ovarian stimulation or stunted follicular growth is a frequent observation with CC. Inappropriate pregnancy rate & inadequate pregnancy outcomes are also observed with CC. The next approach of ovulation induction in CC resistance cases is using continuous Gonadotropin but it has many disadvantages such as high treatment cost, multi follicular development leading to multiple pregnancy, OHSS and frequent shifting of cycle to IVF-ET treatment. Letrozole induces folliculogenesis by releasing H-P axis from tonic inhibitory effect of estrogen & by augmenting gonadotropin secretion. It helps in follicular development without any adverse effect on the peripheral estrogen sensitive tissues. Adding few ampoules of gonadotropin at interval along with letrozole increases FSH at follicular receptor level & produces good quality oocyte. The purpose of the study was: -To evaluate the efficacy of combined Letrozole & 3 doses of gonadotropin in CC resistant IUI cases. -To compare the efficacy and cost effectivity of this protocol with continuous gonadotropin therapy. This RCT was conducted in a tertiary infertility care centre from July 2017 to January 2019. Total 108 anovulatory PCO women in the age group 20 to 36 years who had previous ≥3 failed treatment cycles with CC were randomly divided into Group A (Letrozole plus 3 doses gonadotropin group) & Group B (Continuous gonadotropin group) comprising 54 patients in each group. 2 blood samples from all the patients on Day2 of cycle and on the Day of hCG triggering were analyzed for endocrine profile. Patients in gr A were studied for total 96 cycles (n = 96) who received tab Letrozole 5 mg daily from D2 to D6 and injection U-FSH- HP (75 IU) on D2, D5 and D8 of cycle. Patients in gr B were studied for total 84 cycles (n = 84) & received continuous gonadotropin (U-FSH- HP, 75 IU) starting from D2 of cycle. Folliculometry was started from D9 of cycle & ovulation triggering was done by hCG when dominant follicle reached ≥ 18 mm. Single IUI was performed with documented ovulation. Both groups were evaluated in respect of terminal endocrinological profile, number of follicles, ovulation rate, pregnancy rate & outcome, adverse effects & cost effectivity. Demographic & baseline endocrine profile was comparable. In Gr A & B, mean no of follicles and average terminal estradiol level were 1.8 ±0.6 Vs 4.2 ± 0.8 (p< 0.05) and 266 ± 46 Vs 756 ± 84 pg (p< 0.001) respectively. Ovulation rate and pregnancy rate in both groups were 83.3% Vs 90.5% (p = 0.157) and 18.8% Vs 20.2% (p = 0.774) in Gr A & B respectively. In Gr B, 3 patients (3.6%) developed OHSS and 4 patients (4.8%) needed shifting of cycle to IVF-ET whereas no such incidents happened in Gr A. The average cost per cycle was significantly less in Gr A than Gr B. The combined therapy with Letrozole and 3 doses of gonadotropin is a cost effective treatment protocol in CC resistant PCOS patient before proceeding to costly continuous gonadotropin therapy without any significant difference in ovulation and pregnancy rate.