For younger women facing diminished ovarian reserve, the choice of stimulation protocol during IVF may carry more weight than previously assumed. A clinically meaningful gap in live birth outcomes between two widely used approaches suggests that protocol selection deserves more individualized scrutiny — particularly for patients whose low anti-Müllerian hormone levels already signal a steeper reproductive challenge.
This retrospective cohort study examined nearly 5,000 fresh cleavage-stage embryo transfer cycles performed between 2016 and 2024 at a single center, focusing on women under 35 with AMH below 1.2 ng/mL — a threshold associated with poor ovarian response. After propensity score matching to balance 1,422 cycles per group, the GnRH agonist (long) protocol produced a clinical pregnancy rate of 55.0% versus 47.7% with the GnRH antagonist protocol, and a live birth rate of 41.7% versus 31.7%. Multivariate logistic regression confirmed the agonist protocol conferred approximately 1.25 times greater odds of clinical pregnancy (OR 1.25; 95% CI: 1.02–1.52). Rates of ectopic pregnancy, early miscarriage, and preterm birth did not significantly differ between groups.
These findings run somewhat counter to the growing clinical preference for antagonist protocols, which are favored for their shorter duration, lower medication burden, and reduced ovarian hyperstimulation syndrome (OHSS) risk — particularly in poor responders who are already considered low-OHSS risk. The live birth differential of roughly 10 percentage points is not trivial in reproductive medicine, where each cycle carries substantial emotional and financial cost. However, this is a single-center retrospective design, meaning unmeasured confounders and center-specific laboratory practices could inflate the apparent benefit. The study also focuses exclusively on fresh cleavage-stage transfers, leaving open questions about whether the advantage persists with blastocyst transfers or frozen cycles — the latter now favored by many programs for poor responders. This finding is hypothesis-generating and warrants prospective validation before influencing broad practice changes.