There are several thing to consider.
Will the fan be switched separately, or tied to the lighting.
Is the bathroom heated.
Sloping the duct down will prevent condensation from flowing back into the room, but so will running the fan for an additional time after the room is occupied. However, the down slope can also cause moisture to accumulate at the low point and eventually rote the ducting.
In a short run 4" or 6" may make little difference, however the loss of efficiency can be attributed to the size of the duct and the blower's ability to overcome it.
Using the two 45's is a step in the right direction. Around here, I only us rigid ducting for vented appliances.