Causal inference indicates that poor responders have similar outcomes with the antagonist protocol compared with flare.

Objective: To use causal inference to investigate whether the flare or antagonist protocol is better for poor responders going through controlled ovarian stimulation.

Design: A retrospective study.

Setting: Retrieval cycles from the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System.

Patients: Patients in the United States underwent autologous in vitro fertilization cycles from 2014 to 2019 using either the flare or antagonist protocol.

Intervention: Not applicable.

Main Outcome Measure: Primary outcomes included oocytes retrieved, fertilized oocytes (2PNs), blastocysts, the cumulative live birth rate (CLBR), and cycle cancelation rate.

Results: After propensity score matching, patients with a predicted poor response (antimüllerian hormone, <0.5) on their first in vitro fertilization cycle had similar outcomes on the antagonist protocol (CLBR of 14.2%, 95% confidence intervals [CIs]: 13.6%, 14.8%) compared with flare (CLBR of 13.6%, 95% CIs: 12.4%, 14.8%). We evaluated patients undergoing a second cycle after having a poor response (<4 oocytes retrieved) on their first cycle. Patients in the antagonist-to-antagonist group had a similar change in outcomes between the first and second cycles (average CLBR improvement of 13.9%, 95% CIs: 12.1%, 15.6%) compared with the antagonist-to-flare group (average CLBR improvement of 14.4%, 95% CIs: 10.9%, 18.3%). In addition, patients in the flare-to-antagonist group had a similar change in outcomes between the first and second cycles (average CLBR improvement of 10.4%, 95% CIs: 6.6%, 14.5%) compared with the flare-to-flare group (average CLBR improvement of 9.0%, 95% CIs: 5.1%, 13.4%).

Conclusion: Poor responders have similar outcomes on an antagonist protocol compared with a flare protocol for both the first and second cycles.