A more specialized form of IVF is ICSI, or Intra-Cytoplasmitic Sperm Injection. This form of injection fertilization involves inserting one sperm cell into an ovum using an ultra-fine needle. This technique is recommended if other techniques fail, such as IVF. ICSI provides a solution for serious male fertility problems. Even men who have virtually no sperm cells or none at all in their ejaculate can still become fathers using this technical route. If the seminal fluid contains no sperm cells, it is still possible to take them straight out of the testes using a testis biopsy or testicular extraction (TESE) and then to freeze them for future use.

The notable possibilities of ICSI do however also present concerns about the safety of this technique. It is suspected that weak or imperfect sperm cells do not have the opportunity to fertilize the ovum in normal fertilization. Exactly how this happens is now known but, in ICSI, these selection mechanisms are somehow partially circumvented. At the moment, no method exists for detecting and excluding "bad" sperm cells.

Some people fear that the ovum could be damaged during insertion of the sperm cell or that foreign substances could find their way into the ovum and that this would then cause foetal abnormalities.

For the time being, there is no evidence that ICSI does increase the risk of congenital abnormalities. The risk of having children with a chromosomal abnormality is slightly higher following ICSI (1.8%) compared to the risk for children born following natural conception or after IVF (1%). For this reason, the present position of the LUFC is as follows: IVF where possible and ICSI when necessary, if IVF is impossible as a result of insufficient motile or normal sperm cells.

Every IVF or IVF/ICSI treatment is followed by a discussion with the couple of the progress and result of the procedure and about the plans for possible further attempts or for (temporarily) stopping treatment.