In one of the largest analyses to date examining ovarian stimulation strategies in young women at high predicted risk of low oocyte yield, researchers report that the gonadotropin-releasing hormone (GnRH) antagonist protocol delivers markedly superior oocyte retrieval outcomes compared with progestin-primed ovarian stimulation (PPOS).
The retrospective cohort study evaluated 2,068 first-cycle IVF/ICSI patients aged 35 years or younger, all classified as high risk for low oocyte yield using a validated, multi-parameter nomogram.
GnRH Antagonist Protocol Delivers Higher Oocyte Numbers
After propensity score matching, the GnRH antagonist protocol consistently outperformed PPOS across multiple statistical approaches, including Bayesian analyses. Patients in the antagonist group retrieved an average of 8.3 oocytes versus 5.3 with PPOS, with overwhelming statistical support (BF₁₀ > 10²⁸). The incidence of low oocyte retrieval (<10 oocytes) was also significantly reduced (65.2% vs. 86.0%).
Comparable Embryology Outcomes
Despite major differences in oocyte yield, fertilization and embryo quality were similar between the two protocols. These findings highlight that the benefit is specific to oocyte number rather than downstream embryologic performance.
Risk-Stratified Insights
Subgroup analyses revealed that the antagonist protocol maintained its advantage across low- to mid-risk strata, with median odds ratios ranging from 0.30 to 0.57. Interestingly, in the highest-risk subgroup, PPOS appeared to perform as well as, or marginally better than, the antagonist approach, suggesting protocol selection may need to be tailored at the extremes of risk.
Individualizing Stimulation Strategies
Taken together, the data support risk-adapted ovarian stimulation, with GnRH antagonist protocols offering the most reliable oocyte yield for the majority of high-risk young patients. The authors note that these findings may guide more personalized treatment planning and improve overall clinical outcomes in a population where maximizing oocyte number is critical.
Reference
Teng Y et al. Gonadotropin-releasing hormone antagonist protocol is associated with higher oocyte yield in young women at high risk for low oocyte retrieval: a retrospective study using three statistical methods. Fertil Steril. 2025;124(6):1255-64.
