Geraedts J.P.M.
Department of Molecular Cell Biology and Genetics, Universiteit Maostricht, P.O. Box 1475, 6201 BL Manstricht, The Netherland
Introduction: Of all human conceptions, only 25-30% progress successfully to delivery. Most probably, high embryonic mortality has contributed to the evolution of the human species. Early pregnancy failure ultimately results in reproductive success. This paradox can be explained by assuming that embryonic mortality leads to increased likelihood that already existing offspring reach adulthood and sexual maturity thereby transmitting their genes to the next generation. Chromosome abnormalities constitute the major cause of embryonic loss.
Materials and methods: Chromosome studies on early cmbryos are difficult (o carry out due to the limited number of (dividing) cells. More and more. classical karyotyping is being replaced by studies of non-dividing cells using molecular techniques such as in-situ hybridization. For the future, developments such as whole genome amplification in combination with comparative genome hybridization are promising.
Results: It has been estimated that the contribution of chromosomally abnormal oocytes and spermatozoa to aneuploid zygotes is ~26 and 7 % respectively. Triploidy results from fertilization abnormalities such as dispcrmy. Tetraploidy results from division errors after fertilization. About 40% of all zygotes are chromosomally abnormal. Mitotic abnormalities occur frequently after fertilization during the second or later cleavage divisions and result in early embryonic mosaicism. In theory, meiotic non-disjunction causes monosomic and trisomic conceptions in equal proportions. In preimplantation embryos, autosomal monosomies are still present, but most probahly these embryos die before or around the time of implantation. After implantation, cytogenetic assessment of human embryos is mainly achieved by the study of spontaneous ahortions. Chromosome abnormalitics are encountered in the majority of cases. Except trisomy 1, which is lethal very early, all autosomal trisomies have been observed after implantation. Only three autosomal trisomies have an estimated survival of > 1%: trisomies 13, 18 and 21. Even the most frequent autosomal trisomy at birth (trisomy 21) shows ~80% prenatal selection. In > 90% cases. autosomal trisomy in human abortion results from maternal meiotic errors and. for all chromosomes except the largest, the error rates increase with maternal age. Trisomy 16 is the most frequent trisomy. Its rate resembles that of monosomy X (Turner's syndrome), which is lethal in 98 % of cases. A minority of cases shows structural chromosome abnormalities, mainly translocations and inversions. About half the number in this group results from karyotypic abnormalities in the father, or more frequently, the mother. This is the most important reason for recurrent miscarriage
Conclusion: Cytogenetic analysis of early human embryos is important for the study of formation, transmission and aetiology of chromosomal abnormalities after natural conception and medically-assisted reproduction.