Depends on what you mean by difficult.
With a dual ring flash and hand held, its heavy. Focal plane is narrow and so difficult to get right on a single shot. However, I typically shoot multiple shots once I decide on the composition and the desired plane of focus. Lately I have been using it with a monopod that has made it a fair bit easier to handle. Compare it to shooting a 100 both set for 1x, and you will find no significant difference. Yes the 100 gives you a bit more working distance, 35mm to be exact, but whether thats an advantage or not depends on the subject. Yes the 100 is autofocus, but you'll rarely use autofocus in macro work anyhow.
In all I use the 65, 100, 180, 90 TS-E, and 300 f4 for macro work with the latter two used with extensions. They differ in weight (a big factor in handheld macro work), working distance (an issue with skittish insects). But really none are more difficult than any other with perhaps the exception of the 90 TS-E, and perhaps my difficulty here is simply my current lack of experience with this lens.
As for difficulty in use in the sense of making esthetically pleasing images, well that all depends on your creativity, vision, and skill. No different than any other lens in general but here the art is extreme extraction, and in most of the art work I do, abstraction.
