The Principles of Clinical Cytogenetics - Extra Materials - Springer

Cytogenetics of Spontaneous Abortion 341
Tharapel and colleagues reviewed published surveys of couples with two or more pregnancy losses
(8208 women and 7834 men) and found an overall prevalence of major chromosome abnormalities of
2.9% (112). They go on to suggest that even with normal parental chromosomes, prenatal diagnosis
should be offered because of the high incidence of chromosomal abnormalities in spontaneous pregnancy
loss. Drugan and colleagues identified five anomalous fetuses, including one trisomy 18, two
trisomy 21, one trisomy 13, and one monosomy X fetus among 305 couples with recurrent pregnancy
loss (113). This 1.6% risk is greater than the risk usually cited for amniocentesis. A control
group of 979 patients revealed only three abnormalities (0.3%), all sex chromosome aneuploidies.
This would suggest an increased risk for nondisjunction among couples experiencing repeated pregnancy
failure. Their conclusion is that prenatal diagnosis is sufficiently safe and the risk for an abnormal
result is sufficiently high to justify offering prenatal diagnosis to couples with a history of two
losses. Although this conclusion is based on a relatively small sample size and not all obstetrical
caregivers would agree, a discussion of risks and benefits of prenatal diagnosis would appear to be
justified in this patient population.
Although considerable advances have been made in understanding the causes underlying pregnancy
failure and there is considerable hope for more specific therapies for couples experiencing
nonchromosomal losses, there is unfortunately little to offer the couple who might be at increased
risk for cytogenetically abnormal pregnancies. When a rearrangement is incompatible with normal
pregnancy outcome (such as an isochromosome 21), use of donor ova or sperm might be an option.
The issues are not so clear for the couple with recurrent aneuploidy or polyploidy.
Preimplantation assessment of the fetal karyotype using FISH might be a consideration for some
patients undergoing in vitro fertilization (IVF) for other reasons. Simultaneous use of probes for
chromosomes 13, 18, 21, X, and Y can enhance the likelihood of transfer of normal embryos; however,
some mosaic aneuploid conceptions and aneuploidy for other chromosomes would still be
missed (114). It is important to remember that the majority of embryos with cytogenetic abnormalities
will be lost spontaneously, thus the unknowing transfer of cytogenetically abnormal embryos
potentially contributes to the less than optimal success rate for IVF procedures. Better methods for
identifying chromosomally normal embryos for transfer are needed (115).
SUMMARY
Humans experience a wide range of chromosomal abnormalities at conception. The incidence is
surprisingly high when compared with other mammals, such as the mouse. When considering pregnancy
loss in this context, spontaneous abortion can be seen as a means of “quality control” in an
otherwise inefficient reproduction system (14). Our understanding of the mechanisms involved in
meiosis, fertilization, and mitosis is still quite limited, and the factors affecting survival of the embryo
are not yet fully understood. Maternal age appears to increase the incidence of abnormal conceptions
but might also decrease the efficiency of this control process.
Although our understanding of pregnancy loss is limited and we cannot fully predict risks, we can
attempt to offer patients some explanation as to why a given pregnancy has failed and whether there
is any treatment that might improve chances for future success. We can also make prenatal diagnosis
available in those cases in which there is increased risk for cytogenetic abnormalities or when additional
reassurance of a normal fetal karyotype is needed. It is important to keep in mind that even
with a history of a chromosomally abnormal pregnancy, most couples have a good chance for a
subsequent successful outcome.
REFERENCES
1. Kay, J. (1987) Pregnancy loss and the grief process. In Pregnancy Loss: Medical Therapeutics and Practical Considerations
(Woods, J.R. and Esposito, J.L., eds.), Williams & Wilkins, Baltimore, MD, pp. 5–20.
2. Hager, A. (1987) Early pregnancy loss: miscarriage and ectopic pregnancy. In Pregnancy Loss: Medical Therapeutics
and Practical Considerations (Woods, J.R. and Esposito, J.L., eds.), Williams & Wilkins, Baltimore, MD, pp. 23–50.