Intracytoplasmic sperm injection (ICSI) has become the most commonly used method of
fertilization in assisted reproductive technology. The primary reasons for its popularity
stem from its effectiveness, the standardization of the procedure, which means that
it can easily be incorporated into the routine practice of fertility centres worldwide,
and the fact that it can be used to treat virtually all forms of infertility. ICSI
is the clear method of choice for overcoming untreatable severe male factor infertility,
but its (over)use in other male and non-male factor infertility scenarios is not evidence-based.
Despite all efforts to increase ICSI efficacy and safety through the application of
advanced sperm retrieval and cryopreservation techniques, as well as methods for selecting
sperm with better chromatin integrity, the overall pregnancy rates from infertile
men remain suboptimal. Treating the underlying male infertility factor before ICSI
seems to be a promising way to improve ICSI outcomes, but data remain limited. Information
regarding the health of ICSI offspring has accumulated over the past 25 years, and
there are reasons for concern as risks of congenital malformations, epigenetic disorders,
chromosomal abnormalities, subfertility, cancer, delayed psychological and neurological
development, and impaired cardiometabolic profile have been observed to be greater
in infants born as a result of ICSI than in naturally conceived children. However,
as subfertility probably influences the risk estimates, it remains to be determined
to what extent the observed adverse outcomes are related to parental factors or associated
with ICSI.