When Progesterone USP (bio-identical) is applied to the skin, it gets into circulation and avoids first pass metabolization by liver. When the appropriate solvent is used to dissolve the Progesterone USP powder, the progesterone is transported through the liver.
Steroidogenesis refers to the process whereby the body makes steroids for itself. The key jump - from cholesterol to pregnenolone - is facilitated with Vitamin A and thyroid (T3).
Know a couple who were trying to conceive, after suppressing her fertility with fake hormones (and an IUD) for maybe 8+ years. Lots of miscarriages. They eventually went for IVF, which didn't work either. They gave up and started getting their house ready for adoption. Then they got surprised. I don't think she used topical Progesterone, just the megadoses in Prometrium (liver can't destroy it all on the first pass).
Best wishes to you & your wife.