Impact of letrozole co-treatment in an antagonist protocol for IVF/ICSI: a retrospective study

The present study aimed to investigate the impact of combined use of letrozole in an antagonist protocol during IVF on live birth outcomes and to assess the safety of letrozole in terms of maternal and neonatal complications.

This retrospective cohort study included women undergoing IVF/ICSI and fresh embryo transfer (ET) treatment with and without letrozole co-treatment from 2007 to 2021 at Shanghai Ninth People's Hospital (Shanghai, China). The primary outcome was the live birth rate, while the incidences of maternal and neonatal complications were secondary outcomes. Logistic regression models were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the analyzed outcomes. Sensitivity analysis was performed using a propensity score-based patient-matching (PSM) model, an inverse probability weighting (IPW) model, logistic regression models with women undergoing their first IVF-ET cycle, and subgroup analysis.

Of the 4780 women enrolled in the study, 3887 underwent an antagonist protocol for ovarian stimulation, while 893 received letrozole co-treatment. In this cohort, letrozole co-treatment demonstrated comparable live birth rates to the use of antagonist protocol alone (logistic regression: aOR, 0.88; 95% CI, 0.71-1.08; PSM: aOR, 0.97; 95% CI, 0.77-1.22; IPW: aOR, 0.88; 95% CI, 0.71-1.10). Notably, individuals with a body mass index (BMI) exceeding 24 and those with high ovarian response experienced higher live birth rates under the letrozole co-treatment regimen (BMI ≥ 24: aOR, 1.85; 95% CI, 1.14-3.00; high response: aOR, 1.60; 95% CI, 1.02-2.50). Letrozole co-treatment was also associated with decreased risks of gestational diabetes (aOR, 0.34; 95% CI, 0.15-0.69) and small for gestational age (SGA) fetuses (aOR, 0.42; 95% CI, 0.22-0.75) in fresh ET cycles. These finding were robust in both PSM and IPW models.

Our findings suggested that letrozole co-treatment in antagonist protocol for IVF/ICSI was associated with a comparable live birth rate following fresh ET. Further prospective randomized studies are needed to verify our results.