Age-stratified analysis of euploidy rates in Progestin-Primed Ovarian Stimulation (PPOS) utilizing micronized progesterone or dydrogesterone versus GnRH analogues.

PURPOSES: This study aims to analyze the euploidy rates of PPOS utilizing micronized progesterone and dydrogesterone in comparison to conventional controlled ovarian stimulation (COS) protocols in pre-implantation genetic testing for aneuploidy (PGT-A) cycles stratified by age cohorts. METHODS: This was a retrospective study including 2897 PGT-A cycles from a single reproductive medicine center. Study groups were categorized by different COS protocols, including PPOS (micronized progesterone), PPOS (dydrogesterone), GnRH-agonist, or GnRH-antagonist, and further sub-grouped into < 35 years, 35-37 years, 38-40 years, and > 40 years. Data about baseline characteristics, protocols and embryonic outcomes were analyzed. Multivariate regression analysis and adjustment by inverse probability of treatment weighting (IPTW) were performed to investigate the correlation between COS protocols and euploidy rate per biopsied blastocyst. RESULTS: Before stratified analysis and adjustment, the PPOS (dydrogesterone) group had significantly higher age, lower AMH level and fewer AFC than the PPOS (micronized progesterone), the GnRH-a and GnRH-Ant groups. Euploidy rate per COC, per MII oocyte and per biopsied blastocyst were lowest in the PPOS (dydrogesterone) group, followed by the PPOS (micronized progesterone) group. In subgroup analysis, the euploidy rate showed great disparity in different age groups and declined sharply every three years. All COS protocols were statistically comparable with respect to euploidy rate across all age cohorts. Regression analysis and IPTW adjustment revealed age as the sole factor affecting euploidy rates, with ovarian stimulation protocols showing no association. CONCLUSIONS: PPOS protocols using micronized progesterone or dydrogesterone were statistically comparable with conventional COS regimens in euploidy rates across all different age groups. Considering the significant impact of age, the necessity of refined age stratification for a more rigorous discussion about the aneuploidy risk of different COS protocols was emphasized.