〔Abstract〕 ObjectiveTo analyze the effects of the Progestin-Primed Ovarian Stimulation (PPOS) protocol on embryo euploidy rate and clinical pregnancy outcomes in infertile patients. MethodsWomen who underwent Preimplantation Genetic Testing for Aneuploidy (PGT-A) cycles were selected as study participants (a total of 656 cycles and 3081 blastocysts). Participants were divided into two age groups (≤35 years and >35 years) and further stratified by ovarian stimulation protocol: the Progestin-Primed Ovarian Stimulation (PPOS) group (n=48 and 60, respectively), the Luteal Phase Long Protocol (LP) group (n=160 and 57, respectively), and the Gonadotropin-Releasing Hormone Antagonist Protocol (AP) group (n=220 and 111, respectively). Baseline characteristics, ovarian stimulation outcomes, and embryo development parameters were compared among the three protocols within each age group. Additionally, clinical pregnancy outcomes of the first frozen embryo transfer (FET) cycle were compared. The primary outcome measure was the embryo euploidy rate. Results1. In the ≤35 years age group, baseline follicle-stimulating hormone (bFSH) levels were significantly higher in the PPOS group compared to the LP and AP groups, and the bFSH/bLH ratio was significantly higher in the PPOS group than in the AP group ( P < 0.05). In the >35 years age group, bFSH levels in both the PPOS and AP groups were significantly higher than in the LP group ( P < 0.05).2. In the ≤35 years group, there were no significant differences in the rates of metaphase II (MII) oocytes, 2-pronuclei (2 PN) fertilization, cleavage, 2 PN cleavage, blastocyst formation, high-quality embryos, or embryo euploidy between the PPOS group and either the LP or AP groups. However, the PPOS group showed significantly lower values for the following parameters compared to the other two groups: total oocytes retrieved, number of MII oocytes, number of 2 PN zygotes, number of cleaved embryos, number of 2 PN cleaved embryos, number of blastocysts formed, number of high-quality embryos, number of high-grade blastocysts, number of transferable embryos, number of cryopreserved embryos, number of biopsied blastocysts, number of euploid embryos, and the rate of obtaining at least one euploid embryo. In the >35 years group, no significant differences were observed among the PPOS, LP, and AP groups in the rates of MII oocytes, 2 PN cleavage, blastocyst formation, or in the number of euploid embryos, euploidy rate, and the rate of obtaining at least one euploid embryo. However, the PPOS group had significantly lower numbers of total oocytes retrieved, MII oocytes, 2 PN zygotes, cleaved embryos, 2 PN cleaved embryos, blastocysts formed, transferable embryos, and cryopreserved embryos compared to the LP group ( P < 0.05). The high-quality embryo rate was significantly lower in the PPOS group than in the AP group ( P < 0.05). The numbers of high-quality embryos, high-grade blastocysts, and biopsied blastocysts were significantly lower in the PPOS group than in both the LP and AP groups ( P < 0.05). Notably, the 2 PN fertilization rate was significantly higher in the PPOS group than in the AP group, and the cleavage rate was significantly higher in the PPOS group than in both the LP and AP groups ( P < 0.05).3. No significant differences were found among the three groups in the biochemical pregnancy rate, clinical pregnancy rate, live birth rate, early miscarriage rate, and late miscarriage rate following the first FET cycle ( P ≥ 0.05). ConclusionCompared to the other two protocols, the PPOS protocol does not significantly affect embryo euploidy or clinical pregnancy rates. However, in freeze-all cycles with PGT-A, the PPOS protocol does not reduce the rate of chromosomally normal embryos but may decrease the total number of available embryos. It may not be the optimal choice for younger women, but it can be considered as a viable option for women of advanced maternal age.