I'd like to leave my pyperformance (x64) results here.
cpython: ae5259171b8ef62165e061b9dea7ad645a5131a2 (2021-8-23)

1) release + CFG      : 1.00x

2) release + CFG,/Ob3 : 1.05x faster | 41 faster
                                     |  9 slower
                                     |  8 not significant

3) release (default)  : 1.07x faster | 52 faster
                                     |  4 slower (regex_v8,
                                     |            regex_effbot,
                                     |            nbody,
                                     |            hexiom)
                                     |  2 not significant

4) release + /Ob3     : 1.11x faster | 56 faster
                                     |  1 slower (regex_v8)
                                     |  1 not significant (regex_dna)

5) PGO + CFG          : 1.15x faster | 53 faster
                                     |  2 slower (regex_dna,
                                     |            pidigits)
                                     |  3 not significant

6) PGO + CFG,/Ob3     : 1.15x faster | 54 faster
                                     |  1 slower (regex_dna)
                                     |  3 not significant

7) PGO (default)      : 1.21x faster | 56 faster
                                     |  1 slower (regex_dna)
                                     |  1 not significant (regex_effbot)

8) PGO + /Ob3         : 1.21x faster | 57 faster
                                     |  1 slower (regex_dna)
                                     |  0 not significant