I.S. (Pronounced Aiesu in Japanese) is not your everyday manga. This manga strictly deals with cases of intersexuality. I.S. stands for Inter Sexuality.
This manga deals with very serious issues with intersexuality people. The pain they go through, the troubles they confront, and ultimately their inability to reproduce and even find a partner who will accept them as they are - It's all there in a form of manga.
The first volume deals with two separate cases, from volume 2 onwards it deals with a family and how the child deals with its condition and surroundings.