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At least 50% of the clinically recognized pregnancies that are lost in the first trimester have a major chromosomal abnormality when the products of conception are examined. In pregnancies lost later in gestation there is also a high rate of chromosomal abnormality, roughly 30% in the second trimester and 5% in the third trimester.

The “largest single class” of chromosomal abnormality found in spontaneous abortions are the autosomal trisomies (roughly 50% of abnormal specimens), some of which reveal a maternal age effect. Monosomy X is the “single most common” chromosomal abnormality found in spontaneous abortions (roughly 25% of abnormal specimens), which usually occurs due to a loss of the paternal sex chromosome (Y chromosome) and is not more common with advancing maternal age.

Available Drawings: Available Photos: Avilable Case Reports:

Infertility specialists universally accept certain chromosomal abnormalities as a cause for recurrent pregnancy loss. Fortunately, these major chromosomal abnormalities are uncommon. They may occur within either the maternal or paternal chromosomes. The overall incidence of chromosomal abnormality as the cause of recurrent pregnancy loss is low (less than 5% of couples with recurrent losses). The abnormalities associated with recurrent pregnancy loss include

1. Translocations, which are either “Robertsonian” (the result of centric fusion following the loss of the short arms of two participating chromosomes and possibly one of the centromeres) or “reciprocal” (interchanges of genetic material among different chromosomes following the breaking off of pieces of chromosomes such that the total chromosome complement may still contain all of the genetic material).

Available Drawings: Available Case Reports:

2. Inversions, which are either “paracentric” (rearrangements in the genes on a chromosome following the breaking off of a piece of chromosomal material and its reattachment in a different order, not including the centromere) or “pericentric” (rearrangements within a chromosome that do include the centromere).

Available Drawings: Available Case Reports:

3. and possibly recurrent aneuploidy (numeric chromosomal abnormality), where given couples appear to show a predisposition toward particular types of chromosomal abnormalities (the most common being recurrent trisomies) and couples with a loss showing an abnormal chromosomal complement (in the products of conception) for an initial pregnancy loss have a much greater chance of another abnormal chromosome analysis (in the products of conception) if they suffer another loss (up to 80%).

Available Drawings: Available Case Reports:

Robertsonian translocations

1. Involve only the acrocentric chromosomes (consisting of the “D” chromosomes 13, 14 and 15 and the “G” chromosomes 21 and 22) where the lost short arms of the involved chromosomes appear to only contain genes for ribosomal RNA (which does not result in malformations so that the carriers appear totally healthy),

2. May involve the same chromosomes, such as 13/13 or 21/21, where there is no chance for a normal offspring. A 21/21 translocation (seemingly the worst case) results in the offspring only having either a lethal monosomy (50%) or Down's syndrome (50%),

3. May result from a 21/D or 21/22 translocation where there are theoretically 6 possible combinations with three of these being lethal and of the other three there is an equal 33% chance of having a Down's syndrome, a balanced translocation (normal appearing as with the parent carrying the translocation) or a normal set of chromosomes. In reality, for an unknown reason, experience has shown that there is only about a 10-15% chance of Down's syndrome if the mother is the carrier and 2-5% chance of Down's syndrome if the father is the carrier, while the balanced translocation rate is about 50% in liveborns.

Reciprocal translocations

1. are rearrangements between chromosomes that do not necessarily entail loss of genetic material in the “parent” (they appear normal),

2. may be passed on to the offspring such that small pieces of genetic material are either added to or subtracted from the total chromosome complement (an unbalanced translocation) of the offspring. This can be either lethal or very damaging (usually resulting in severe mental retardation and major anomalies),

3. in reality, experience has shown that there is only a 10-15% risk of an unbalanced translocation in offspring independent of whether the mother or father is the carrier

Paracentric inversions

1. are very difficult to detect on chromosome analysis,

2. are less common than pericentric inversions,

3. are rare causes for recurrent pregnancy loss, and

4. may result in early pregnancy loss

Pericentric inversions

1. are usually easy to identify on chromosome analysis,

2. are detected in about 1 in 1000 couples with recurrent pregnancy loss,

3. are more likely to result in abnormal crossover of genetic material during meiosis to yield unbalanced offspring,

4. females with a pericentric inversion have about an 8% chance, while males with a pericentric inversion have about a 5% chance, of an abnormal liveborn (depending on the specific inversion detected),

5. pericentric inversions can develop as the cells taken for chromosome analysis are grown in culture so that the lab should be contacted whenever an inversion is reported to identify the labs experience with similar inversions (to determine the likelihood of culture artifact)

Whenever a couple has suffered three (or if desired by the couple, two) spontaneous abortions, an investigation of the chromosomes for both of the female and male is indicated. This investigation is normal 95% of the time. If an abnormality is identified, prompt consultation with an experienced human geneticist is indicated since the theories and actual experiences in this field are complex and constantly changing. Preconceptional counseling and planning with respect to prenatal diagnosis is also important. Unfortunately, there is no available treatment to “fix abnormal chromosomes” at this time.

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