איקסי

ברגע שמבצעים ICSI שוללים למעשה את הבררה הטבעית, בה אחד מקרב מליוני זרעונים מצליח להפרות את הביצית. לאחרונה התפרסמו מחקרים שקושרים את ICSI עם יותר מומים מולדים, אם כי יש גם מחקרים שמורים אחרת. ראי סקירה קצרה שהתפרסמה רק בשבוע שעבר בעיתון בריטי יוקרתי: BMJ 2002;325:117-118 ( 20 July ) Health risks in babies born after assisted reproduction Risk of anomalies, low birth weight, and multiple pregnancies may be increased Parents who conceive after fertility treatments would like to know if their children are at excess health risks compared with children who have been conceived naturally. They would like studies to be done to monitor outcomebut not necessarily on their own children. Outcome studies of in vitro fertilisation are relatively few to date and hampered by difficulties such as high cost, ethical considerations, recruitment of appropriate controls, and unwillingness of some parents even to tell their children how they were conceived, let alone bring them for assessments. Early studies were small, uncontrolled, and had other methodological errors. In contrast the pace of advances in the treatment of infertility has been rapid. The development of embryo cryopreservation has been followed by potentially more hazardous techniques such as intracytoplasmic sperm injection and extended embryo culture. Other techniques entail manipulating the embryo in vitro by assisted hatching and preimplantation genetic diagnosis, a diagnostic procedure. The eldest individuals born after in vitro fertilisation are now young adults, and 1% of children in developed countries are now conceived through in vitro fertilisation. Ultimately when this first generation of children born after in vitro fertilisation grow up, they will become a sizeable subgroup of the population. It is therefore regrettable that it has taken 20 years before an attempt was made to quantify the risk of congenital anomalies to children conceived by in vitro fertilisation.1 Other recent studies investigating this risk after a more invasive methodintracytoplasmic sperm injectioninclude the reassuring series by Bonduelle, which quantified risk only in comparison with babies conceived by in vitro fertilisation but not with babies conceived naturally.2 This series did not adjust for the inclusion of babies born after pregnancies achieved with different hormonal regimens or take into consideration that intracytoplasmic sperm injection sometimes involved non-ejaculated sperm. More recently a report by Hansen et al found an increased risk of anomalies in babies conceived after intracytoplasmic sperm injection, but this study was weakened by efforts to avoid observational bias by relying solely on one blinded paediatrician to determine whether congenital anomalies observed were more likely in babies conceived after this procedure.3 In vitro fertilisation carries an increased risk of higher order births with their attendant risk of major morbidity. Some countries have made efforts to limit replacement of embryos to two (Australia, New Zealand) or even one (Sweden, Finland), whereas other countries have not, despite clear evidence that replacement of three embryos increases only the risk of the birth of triplets but not the overall pregnancy rate.4 The frequency of higher order births (three or more) between 1973 and 1990 increased at about seven times that of singleton births, and, whereas higher order multiple births represented only 1.6% of all births in 1973, they accounted for 3.1% of all multiple births in 1990 in the United States.5 In the United Kingdom, comments by a former chairman of the Human Fertilisation and Embryology Authority have suggested that clinics responsible for the births of triplets due to replacing three or more embryos should contribute to their excess costs of care on the NHS. Couples who have waited many years to conceive may not believe the counsellor when told of a risk of triplets because the chance of having any baby seems so remote. Other critical issues seem to be the risk of higher perinatal morbidity (related largely to complications of multiple pregnancy), the longer term risk of neurodevelopmental disadvantage, and the postulated risk of the in vitro environment causing an increase of diseases affected by genomic imprinting, such as Beckwith-Wiedemann syndrome or cancers such as osteosarcoma. Whether children born after in vitro fertilisation have normal fertility will be a sensitive issue to investigate. Published studies on young children conceived after in vitro fertilisation, embryo cryopreservation, and intracytoplasmic sperm injection have been generally reassuring.6-8 A report from the United States seems to confirm that, by itself, singletons born after in vitro fertilisation are lighter than their naturally conceived peers.9 Before this it was always assumed that the lower birth weights were an effect of the 20-30% rise in higher order births in this population. Another study from Sweden suggests that higher risks of cerebral palsy are not just due to the increase in multiple births.10 No meaningful studies have investigated the effects of preimplantation genetic diagnosis beyond the neonatal period, although the technique entails major manipulation of embryos by the removal of one or two cells from the embryo at the eight to 10 cell stage (up to 25% of the cell mass). The newer techniques, however, such as transfusion of ooplasm, are not yet addressable (the numbers are too small) and in the United Kingdom not permissible by the Human Fertilisation and Embryology Authority. Children born after in vitro fertilisation will have a very different view of the justification for exposing them to any excess risks, especially if they realise that safety considerations were not a priority for the people who had helped their parents conceive them. What is needed here is a large prospective population based study of the birth registry, with naturally conceived children as controls to start addressing the question of risk definitively. Surely now is the time. Alastair G Sutcliffe, senior lecturer in paediatrics. Centre for Community Child Health, Royal Free and University College Medical School, London NW3 2PF