O-045 ICSI: From ‘this cannot work' to ‘remarkably safe'
Authors: Bergh C 
Published: June 2022

Abstract

ICSI
From “this cannot work” to “remarkably safe”
It is now 30 years since the first child was born after ICSI treatment. Since then there has been an ongoing debate on the use and safety of the technique. Initially, ICSI was used to treat severe forms of male factor infertility but today it is also used to treat mild male factor infertility, mixed male/female infertility, unexplained infertility and fertilization failures. Both the latest European ESHRE report and the global ICMART report reveal an increasing global use of ICSI, with more than 70% of cycles using ICSI. Due to the invasiveness of the ICSI procedure as well as the arbitrary selection of the spermatozoon and genetic and epigenetic parental factors, concerns have been expressed about the health of ICSI children.
While most births after ART are uncomplicated, ART is associated with potential adverse obstetric outcomes for both mothers and infants, including hypertensive disorders of pregnancy, preterm delivery, and low birth weight ART has also been associated with an increased risk of birth defects .Many of these adverse outcomes can be attributed to a higher rate of multiple pregnancies after ART. With the increasing use of single embryo transfer, the multiple pregnancy rate has been significantly reduced but is still unacceptably high in many countries. When comparing ICSI and conventional IVF, most large studies have found similar or lower risks of very preterm and preterm birth, very low birth weight, low birth weight and peri/neonatal mortality in ICSI children. A possible explanation for the better outcome in ICSI singletons may be that in ICSI the majority of the women are reproductively healthy, which could give a more favorable intrauterine environment. Most studies have found an increased rate of birth defects in ART children, ranging between 30% and 70% higher, but with no difference between conventional IVF and ICSI and the different sperm sources used in ICSI do not seem to influence the rate of birth defects negatively. However, the incidence of de novo and inherited sex chromosomal abnormalities in ICSI offspring is slightly higher, which probably relates to the genetics of the infertile couples.
Although children born after IVF and ICSI have a higher risk to be born preterm and with low birth weight they usually catch up during the first years. A large systematic review from Denmark showed no differences in weigh and length up to 22 years of age, between children born after IVF and ICSI and children born after spontaneous conception.
Looking at general physical health similar results are observed for ICSI and IVF-conceived children. Most large cohort studies do not show any increase in childhood cancer in general in ART children and provide no evidence of an increased risk in the ICSI group.
Most studies comparing children up to eight years of age born after ICSI, conventional IVF and spontaneous conception, suggest their neurocognitive development is comparable. Sperm source or individual semen parameters do not affect neurodevelopment. Two recent large studies reporting associations between ICSI and autism and autistic disorders should be interpreted with caution, since the absolute risks of autism and autistic disorders are small. School performances in 15-16 years old adolescences have recently been studied in several large Nordic register studies. Children born after ART performed better in unadjusted analyses but after adjustment, mainly for parental education, these differences disappeared. No differences were observed between ICSI and IVF.
Continuous supervision after ART is needed to ensure safety and quality, especially when new techniques are introduced. National ART registries such as those existing in the Nordic countries enable follow-up studies of ART children and should be encouraged.