Comparison of Combined Letrozole and Clomiphene Citrate With Gonadotropin Microstimulation Protocols on Fertility Outcomes.

Purpose: Large-scale data comparing the effects of combined letrozole (LE) and clomiphene citrate (CC) with gonadotropin (Gn) microstimulation protocols on pregnancy outcomes are lacking. This study aimed to compare the effects of CC + Gn and LE + Gn microstimulation protocols on fertility outcomes.

Methods: A retrospective cohort study was conducted to include infertile patients between January 1, 2018, and December 31, 2022. All patients underwent a microstimulation protocol and treatment was administered using either CC + Gn or LE + Gn. The main study outcomes included clinical pregnancy, miscarriage, and live birth rates.

Findings: Of the 1697 included patients, 875 were treated with CC + Gn, while the remaining 822 were treated with LE + Gn. We noted that CC + Gn was associated with a lower clinical pregnancy rate (odds ratio (OR): 0.324; 95% confidence interval (CI): 0.127-0.829; P = 0.019) and live birth rate (OR: 0.332; 95% CI: 0.112-0.988; P = 0.048) than LE + Gn; however, there was no significant difference between CC + Gn and LE + Gn regarding the abortion rate (OR: 0.523; 95% CI: 0.028-9.720; P = 0.664). Moreover, there were significant differences between the CC + Gn and LE + Gn groups in the number of embryos transferred (P < 0.001), number of frozen embryos (P < 0.001), and number of embryos at the frozen cleavage stage (P = 0.002).

Implications: LE + Gn microstimulation protocol was associated with better fertility outcomes than CC + Gn in terms of clinical pregnancy and live birth rates in patients with infertility.