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Comparative effectiveness of GnRH antagonist, mild stimulation, and PPOS protocols in POSEIDON groups 3 and 4: a retrospective cohort study with entropy balancing

Year: 2026

Type: article

Abstract: Background: Patients classified as POSEIDON groups 3 and 4 are characterized by diminished ovarian reserve and a predicted poor ovarian response. Although GnRH antagonist, mild stimulation, and progestin-primed ovarian stimulation (PPOS) protocols are commonly employed in these patients, high-quality evidence comparing their cumulative live birth rates (CLBR) and embryological outcomes in homogeneous cohorts remains limited. Results: The CLBR per initiated cycle differed significantly among the three protocols (40.9% vs. 28.0% vs. 34.2%, p = 0.016), with the GnRH antagonist protocol outperforming mild stimulation. However, after adjusting for age and baseline FSH, the stimulation protocol was not an independent predictor of CLBR. The GnRH antagonist protocol yielded superior embryological outcomes, with significantly higher numbers of oocytes retrieved, usable embryos, and high-quality embryos, and a lower cycle cancellation rate due to no usable embryos (all p < 0.001). Multivariable analysis identified lower AMH and AFC, but not the protocol type, as independent risk factors for cycle cancellation. Mild stimulation demonstrated a higher premature LH surge rate (9.9%) than both antagonist (1.5%) and PPOS (2.1%) groups ( p < 0.001), and a higher biochemical pregnancy rate (19.1%) than the antagonist group (6.9%, p < 0.001). No significant differences were observed in implantation, clinical pregnancy, or live birth rates after the first embryo transfer. Conclusions: After adjusting for confounders, the GnRH antagonist, mild stimulation, and PPOS protocols resulted in comparable cumulative live birth rates and cycle cancellation rates in POSEIDON groups 3 and 4 patients, despite yielding differences in embryological outcomes. These findings support individualized protocol selection based on patient characteristics and preferences. Trial registration: Clinical trial number: Not applicable.

Source: Frontiers in Endocrinology

DOI: 10.3389/fendo.2026.1969038

Authors: Haiyue Zhao, Yunping Ni, Aiai Wang, Juan Liu, Xinghong Lu, Shan Lu

Institution: Guangdong Provincial Hospital of Chinese Medicine

Language: English

Topic: Reproductive Biology and Fertility

Subfield: Reproductive Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801