Mild controlled ovarian hyperstimulation (COH) protocols combining clomiphene citrate (CC) or letrozole with gonadotropins were introduced as an effective alternative of conventional COH in normal responders undergoing IVF/ICSI. In this case-control study, we compared 41 participants treated with a mild stimulation protocol receiving gonadotropins combined with either CC (n = 24) or letrozole (n = 17) with 71 subfertile participants with matching baseline characteristics, conforming with the same inclusion criteria and treated with a conventional antagonist protocol. Live birth was determined in reduced rates in the study group compared to the control group, reaching marginal statistical significance [4/41 versus 19/71, p = 0.050], as also in the respective number of clinical pregnancies [6/41 versus 22/71, p = 0.054], although the incidence of miscarriage was similar for both groups [2/41 versus 5/71, p = 0.714]. Most of the secondary parameters examined, favored the conventional antagonist protocol. There was no difference in any of the outcomes reported between the three different stimulation groups in post-hoc analysis. Mild stimulation regimens with the aid of either CC or letrozole employing GnRH antagonists do not seem to constitute an equally effective method as compared to the conventional antagonist protocol to be offered in good prognosis subfertile women seeking an induced cycle toward IVF/ICSI.
Keywords: Assisted reproductive techniques; clomiphene citrate; letrozole; mild stimulation; normal responders.