Mental Development of 201 ICSI Children at 1 year of Age
July 1, 1998 4 minutes read
Mental Development of 201 ICSI Children at 1 year of Age
ABSTRACT & COMMENTARY
Synopsis: Most children conceived by intracytoplasmic sperm injection are healthy and develop normally, but there is an increased risk of mild delays in development at 1 year when compared to children conceived by routine in vitro fertilization or natural conception.
Source: Bowen JR, et al. Lancet 1998;351:1529-1534.
Intracytoplasmic sperm injection (icsi) involves the fertilization of a mature oocyte by the injection of a single sperm. The main indication for its use is male infertility. Men with oligoasthenospermia often have microdeletions of the Y chromosome or other subtle chromosomal abnormalities as the cause. The use of genetically abnormal sperm may lead to an increased incidence of chromosomal abnormalities, including Y chromosome deletions and abnormal karyotypes, in the offspring. Further, by selecting a single sperm for injection, the ICSI procedure bypasses the usual process of natural selection that occurs both during natural conception and conventional IVF, resulting in a greater chance of fertilization by a chromosomally abnormal sperm. Also, ICSI produces mechanical disruption of the cell membrane of the oocyte and could introduce extraneous material into the oocyte. Given these concerns and the absence of outcome studies of children, the present study was undertaken to determine if children conceived by ICSI were developmentally normal at 1 year of age. Three groups of children were enrolled prospectively: those conceived by ICSI, those conceived by conventional IVF, and those who were spontaneously conceived. The cohorts were similar for multiple gestation (twins), parental age, and parity. Children were formally assessed using the Bayley Scales of Infant Development at 1 year of age, with children being born prematurely being assessed at 1 year corrected age. There were no group differences for any obstetrical factors, including prematurity. The final cohorts included 92 ICSI children, 86 IVF children, and 82 children naturally conceived. Twins accounted for 78% of the premature births. The analysis controlled for differences among groups in occupation, educational level, and country of origin. There were no significant differences in the incidence of major malformations among ICSI (4.5%), IVF (3.6%), and naturally conceived (3.6%) infants. The mental development at 1 year was lower in ICSI (95.9) than in IVF (101.8) and controls (102.5). This difference in mental development was primarily seen in boys and was not accounted for by twinning or prematurity. Of the children with developmental delay, 15% were from ICSI, 2% from IVF, and 1% from natural conception. The mental development subscale of the Bayley assessed memory, problem solving, and language skills. Bowen and colleagues note that the results of the mental development subscale are felt to be more predictive of long-term outcome than are the motor development results.
COMMENT BY SARAH L. BERGA, MD
This thorough study reveals further cause for concern about the long-term consequences of ICSI. Previous studies had documented that children conceived by ICSI had an increased incidence of paternally transmitted, structural aberrations and sex-chromosome abnormalities (Liebaers I, et al. Lancet 1995;346:1095; In't Veld P, et al. Lancet 1995;346:773). This study now reveals an increased risk of developmental delay in children conceived by ICSI. As the accompanying editorial points out, the introduction of new drugs for human use is preceded by a painstaking, highly regulated, and extremely costly process of testing, first in animals and then in humans (te Velde ER, et al. Lancet 1998;351:1524). No such testing was required for the introduction of ICSI; thus, the outcomes and long-term risks are just beginning to be detected. There apparently is ample cause for concern, but it is not clear what should be done. Certainly, prospective patients should be appraised of the risks identified to date. However, when the risk seemed confined largely to passing along infertility to male offspring, most of my patients were undeterred and wished to proceed. The desire to procreate a biological child is a strong urge for most men with oligoasthenospermia who present for treatment. I believe that the prospect of infertility arouses great anxiety-in part because it threatens psychological death. Further, the anticipation of a powerful loss arouses such a sense of desperation that many couples simply cannot hear cautionary information. Further, there is a literal boom in ICSI in the assisted reproduction realm, as clinics struggle to outdo one another for success rates. This is because, ironically enough, the implantation rates for ICSI and IVF are comparable. To guarantee the availability of fertilized oocytes for transfer, it is tempting to do ICSI routinely and bypass conventional IVF techniques in which 100,000-200,000 sperm are incubated with an oocyte. But, the benefit of conventional IVF is that there is still some selection process for sperm in the sense that one sperm must win the race through the cumulus to fuse with the zona pellucida. We tend to think that the barrier of implantation protects prospective mothers from bearing children with major chromosomal abnormalities, and that is still likely to be the case. But, the present study shows that more subtle abnormalities of the embryo are compatible with implantation. As noted earlier, potential hazards of ICSI include the introduction of genetically abnormal sperm, cytoplasmic damage from the lancing of the zona pellucida, and the potential introduction of foreign material. The only explanation for the observation that developmental delay was more common in ICSI boys than girls, however, is the use of genetically compromised sperm. Patients and physicians alike must keep these concerns uppermost in their minds.
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