Balkan Journal of Medical Genetics

Chromosomal studies of spontaneous abortion specimens are difficult to carry out because: 1) frequently the material is not suitable for cytogenetic preparation, 2) occasionally the abortion product has been fixed in preservative for histological examination, making culture and karyotyping impossible, 3) some specimens that are properly sent to the cytogenetic laboratory appear to be contaminated after the culture has been started, 4) a few specimens do not show any growth because intrauterine death occurred long before the tissue was expelled and removed, 5) the yield from some cultures suffers because of a lack or complete absence of embryonic tissues or membranes, and 6) the culture and karyotype analysis is expensive. Therefore, cytogenetic studies of abortion material are only successful in a minority of cases.

The first chromosomal analysis of spontaneous miscarriage revealed triploid cells in two abortions [53]. Then two XO abortuses were reported [54]. Since then, numerous studies have made it clear that the majority of first- trimester abortions are caused by chromosome anomalies.

The most common abnormality is trisomy, which arises de novo as a result of meiotic non disjunction during gametogenesis in parents with a normal karyotype. The incidence increases with maternal age. Trisomy 16 accounts for 30% of all trisomies. Trisomy for all chromosomes, except chromosome 1, has been observed in spontaneous abortion. Occasionally, double trisomies and tetrasomies are observed. Autosomal monosomies are practically unknown in human miscarriages, but monosomy X is a frequent finding. The abnormality most frequently resulting from abnormal fertilization is triploidy.

Finally, there is a group showing 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 chromosomal reason for recurrent miscarriage [55].

Systematic studies on the chromosomal status of spontaneous abortions [1,56,57] were improved by the chorion villus biopsy technique. This was introduced on a large scale for prenatal diagnosis and also allows direct analysis of well-preserved villus material, evacuated from the uterine cavity in those cases of retained abortion identified by ultrasound examination before any clinical evidence of pregnancy interruption had been obtained [2,58,59]. It has recently become possible to study spontaneous abortions using CGH, even after unsuccessful culture [13].

Only three autosomal trisomies are regularly observed at birth: trisomies 13, 18 and 21. They have an estimated prenatal survival of 3, 5 and 20% respectively. The other autosomal trisomies have an estimated survival to term of less than 1/1,000 [24]. Sex chromosome aneuploidies survive normally with the exception of 45,X which is lethal in about 98% of cases [24]. There is no difference between the ages of mothers of live born trisomic children and those spontaneously aborted.