Extended letrozole regimen versus clomiphene citrate for superovulation in patients with unexplained infertility undergoing intrauterine insemination: A randomized controlled trial

Abstract

BackgroundThe aim of this randomized controlled trial was to compare the efficacy of extended letrozole regimen with clomiphene citrate in women with unexplained infertility undergoing superovulation and intrauterine insemination (IUI).MethodsTwo hundred and fourteen patients with unexplained infertility were randomized into two equal groups using computer generated list and were treated by either letrozole 2.5 mg/day from cycle day 1 to 9 (extended letrozole group, 211 cycles) or clomiphene citrate 100 mg/day from cycle day 3 to 7 (clomiphene citrate group,210 cycles). Intrauterine insemination was performed 36 to 40 hours after HCG administration.ResultsBoth groups were comparable with regard to number of mature follicles (2.24 +/- 0.80 Vs 2.13 +/- 0.76) and the day of HCG administration. Serum estradiol was significantly greater in clomiphene citrate group (356 +/- 151 Vs 822 +/- 302 pg/ml, P = < 0.001) and the endometrial thickness was significantly greater in extended letrozole group (9.10 +/- 1.84 Vs 8.18 +/- 1.93 mm, P = < 0.001).The pregnancy rate per cycle and cumulative pregnancy rate were significantly greater in extended letrozole group (18.96% Vs 11.43% and 37.73% Vs 22.86%, respectively).ConclusionThe extended letrozole regimen had a superior efficacy as compared with clomiphene citrate in patients of unexplained infertility undergoing superovulation and IUI.Trial registrationClinicalTrials.gov, NCT01232075

Dual Ovulation Triggering With Follicle-Stimulating Hormone and Human Chorionic Gonadotropin in Women With Unexplained Infertility Underwent Letrozole Superovulation and Intrauterine Insemination: A Randomized Controlled Trial.

“…The current study reported a clinical pregnancy rate of 25% and a live birth rate of 21.3% for the total letrozolestimulated cycles, regardless of the ovulation triggering protocol; the rates that accord with those formerly stated in various studies evaluated letrozole superovulation in women with UI (table 4) [11][12][13][14][15][16] . However, dual triggering by FSH/hCG compared to hCG alone improved the outcome of Letrozole-stimulated IUI cycles manifested as significantly higher pregnancy rate pre-cycle (12.5% vs. 5.8%: p=0.049) and per-woman (33.33% vs. 16.67%: p=0.049), and a significantly higher live birth rate (29.6% vs, 12.5%; p= 0.039).…”

“…These results agree with numerous studies reported the lower incidence of multiple gestations and OHSS in letrozole-stimulated cycles [11,14,15] . These advantages may be attributed to the short half-life of letrozole with no depletion of estrogen receptors; therefore; the normal central feedback mechanisms remain intact creating a higher probability of monofollicular growth [4] .…”

“…However, dual triggering by FSH/hCG compared to hCG alone improved the outcome of Letrozole-stimulated IUI cycles manifested as significantly higher pregnancy rate pre-cycle (12.5% vs. 5.8%: p=0.049) and per-woman (33.33% vs. 16.67%: p=0.049), and a significantly higher live birth rate (29.6% vs, 12.5%; p= 0.039). The reported pregnancy and live birth rates in the FSH/hCG trigger group are superior to those reported in diverse studies evaluating different letrozole-stimulated IUI protocols in women with UI (table 4) [11][12][13][14][15][16] . To our knowledge, this is the first trial planned to appraise the effect of FSH/hCG dual triggering in letrozole-stimulated cycles in ladies with UI.…”

Clomiphene Citrate versus Letrozole for Ovarian Stimulation in Therapeutic Donor Sperm Insemination

“…Only one study [29] reported significantly higher CPR with letrozole, but the difference could be explained by the very low CPR found with CC (23.07 vs. 10.68%, p < 0.001). Fouda and Sayed [30] , in an RCT of 214 women with unexplained infertility undergoing IUI, compared an extended letrozole regimen (2.5 mg cycle days 1-9) with CC and reported significantly higher CPR with letrozole [30] . The rationale behind the extended letrozole regimen is that it can improve pregnancy rates by inducing multiple ovulations [31] .…”

“…In our study, the number of mature follicles was comparable between the 2 groups, but the number of intermediate follicles was significantly higher in the CC group. Results from studies comparing the number of follicles are heterogeneous, and no correlation with multiple pregnancy rates has been reported [26][27][28][29][30] . We found no difference in the multiple pregnancy rates, confirming the results reported in the literature [25,[28][29][30] .…”