IS (Pronounced Aiesu in Japanese) is not your everyday manga. This manga strictly deals with cases of intersexuality. IS stands for Inter Sexuality.
This manga deals with very serious issues concerning intersexual 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 series is consisted of cases, each dealing with different people - although some cases are much longer and more dramatic than others.
The first volume is about the case of Hiromi and the case of Ryoma. The third case is of Haru and characters related to him.
If you don’t know what intersexuality is, refer to the Wikipedia on Intersex.