Since the birth of Louise Brown, the first test tube baby, in 1978 (1), in vitro fertilization (IVF) has become a well-established treatment procedure for certain types of infertility—including long-standing infertility due to tubal disease, endometriosis, unexplained infertility, or infertility involving a male factor. However, it became obvious that certain couples with severe male-factor infertility could not be helped by conventional IVF. Extremely low sperm counts, impaired motility, and poor morphology represent the main causes of failed fertilization in conventional IVF. To tackle this problem, several procedures of assisted fertilization based on micromanipulation of oocytes and spermatozoa have been. | _10__ Assisted Fertilization Andre Van Steirteghem Centre for Reproductive Medicine Academisch Ziekenhuis Vrije Universiteit Brussel Brussels Belgium INTRODUCTION Since the birth of Louise Brown the first test tube baby in 1978 1 in vitro fertilization IVF has become a well-established treatment procedure for certain types of infertility including long-standing infertility due to tubal disease endometriosis unexplained infertility or infertility involving a male factor. However it became obvious that certain couples with severe male-factor infertility could not be helped by conventional IVF. Extremely low sperm counts impaired motility and poor morphology represent the main causes of failed fertilization in conventional IVF. To tackle this problem several procedures of assisted fertilization based on micromanipulation of oocytes and spermatozoa have been established. These strategies have culminated in intracytoplasmic sperm injection ICSI where a single spermatozoon is directly injected into the ooplasma. In 1992 our group reported the first human pregnancies and births after replacement of embryos generated by this novel procedure of assisted fertilization 2 . Since then the number of worldwide centers offering ICSI has increased tremendously as has the number of treatment cycles per year 3 . Because of the widespread application of ICSI as the ultimate and only option for successful treatment of severe male infertility due to impaired testicular function or obstruction of the excretory ducts concern about its efficacy and safety is appropriate. 161 162 Van Steirteghem This chapter surveys the current status of ICSI emphasizing patient selection for ICSI gamete handling prior to microinjection the ICSI procedure and outcome parameters of fertilization and embryo cleavage after ICSI. Furthermore outcome and children s health after IVF and ICSI will be summarized including pregnancy complications major .