Although 50% or more of sporadic pregnancy losses in first trimester are the result of chromosomal abnormalities, these probably account for less than 5% of recurrent early pregnancy losses. There is also usually a difference in the type of chromosomal abnormalities found under these situations. In sporadic losses, the most common causes are ‘nondisjunction events’ in the final cell division that is supposed to equally divide the chromosomal pairs and create eggs or sperm (gametes) that contain only half (23 chromosomes = 22 different ‘autosomes plus 1 ‘sex chromosome’) the normal chromosomal complement (46 chromosomes = 22 pairs of different ‘autosomes’ plus 2 ‘sex chromosomes’, one from each parent).
In nondisjunction events, a pair of chromosomes (autosomes or sex chromosomes) may stick together, resulting in one gamete (egg or sperm) with one too many (24) and one with too few (22) chromosomes. Doing the simple math, if either such gamete combines with a normal gamete containing 23 chromosomes from the other parent, the resulting embryo will have either 45 (a monosomy) or 47 (a trisomy) chromosomes. These events can occur with any of the autosomes or sex chromosomes and most result in lethal combinations of genetic material and pregnancies that are lost early in gestation. However, there are situations in which the pregnancy might survive, the best known being Down syndrome (extra number 21 chromosome), Turner’s syndrome (single X chromosome), other sex chromosomal abnormalities such as 47XXY or 47XYY, and trisomies 18 or 13. In reality, even most of these combinations are lost in first trimester, many are lost in mid or late pregnancy, and almost all trisomy 18 or 13 babies are lost shortly after birth if they manage to survive to delivery.
Chromosomal abnormalities that lead to recurrent pregnancy losses, on the other hand, are usually not monosomies or trisomies resulting from nondisjunction. Instead, they result from gametes that have either too much or too little chromosomal material as a consequence of a parent having a chromosomal ‘rearrangement.’ Under these circumstances a parent has the correct total amount of genetic material, but may have two whole chromosomes (either the same or different chromosomes) stuck together, may have a portion of one chromosome exchanged with a portion of another chromosome (balanced translocations), or have rearrangements of a portion of one chromosome within the chromosome in which that genetic material was originally located (usually these are ‘inversions’). The problem with parents who have ‘chromosomal rearrangements’ is that they have a harder time producing gametes with the correct amount of genetic material. Fortunately, most parents with balanced translocations or inversions will eventually ‘get it right’ but it may be only after many pregnancy losses. Even then, because of ‘crossing over’ events that occur during chromosomal replication, they could end up with a baby that has the ‘right number’ of chromosomes but a very small amount missing (microdeletions) or extra that can still lead to serious problems. Parents who have whole chromosomes stuck together on the other hand cannot produce normal gametes.
Diagnostic testing for parental chromosomal rearrangements is fairly simple, but expensive. It is often one of the first diagnostic tests offered to a couple with recurrent early pregnancy loss, although the yield is low because these account for such a small percentage of the problems. Ideally, both parents should be tested, but if resources are limited, it is often best to start with the mother’s chromosome studies (karyotype) since for reasons beyond the scope of this discussion, if a parental chromosomal rearrangement is the culprit, she is the more likely contributor to the problem under many circumstances. If the products of conception from an early loss have chromosome studies performed and reveal that a parental chromosome rearrangement is likely, parental karyotype testing really should be advanced in the diagnostic studies. Although nothing can be done to correct the problem, genetic counseling is warranted so that parents can be appraised of their risks and their options for a successful pregnancy.