M. Stephenson1
1 University of Chicago Section of Reprod. Endocr. & Infertility, Director, Recurrent Pregnancy Loss Program 5841 South Maryland Avenue (MC 2050) Chicago IL 60637 U.S.A.
Early pregnancy loss, defined as a miscarriage prior to 10 weeks of gestation, is associated with a chromosome error, such as trisomy, monosomy, polyploidy or a structural chromosome rearrangement in 50-70% of such miscarriages (Jacobs PA, Hassold T, 1987; Ohno M, Maeda T, Matsunobu A, 1991). Despite widespread availability of cytogenetic analysis, employing cell culturing followed by banding of metaphase chromosomes, it is not uniformly performed, when indicated. Identification of a chromosome error in a miscarriage provides valuable information for counselling purposes and to determine whether further evaluation is warranted. In addition, with treatment of recurrent pregnancy loss, the identification of a miscarriage with a numeric chromosome error provides evidence that the miscarriage is not the result of a treatment failure, rather, a random event that increases with advancing maternal age. With carriers of a structural chromosome rearrangement, cytogenetic analyses provide vital evidence in regard to whether miscarriages are cytogenetically abnormal, either numeric or unbalanced, or normal, either diploid or balanced structural chromosome rearrangements.
Extraction of miscarriage DNA followed by comparative genomic hybridization, with or without microarray, is being performed increasingly. Such technology has its own inherent advantages and limitations. A comparison of comparative genomic hybridization to conventional cytogenetic analyses revealed that comparative genomic hybridization has a higher success rate (99.7%) and less maternal contamination (Lomax B, Tang S, Separovic E, et al., 2000). Looking to the future, microarray comparative genomic hybridization may identify submicroscopic deletions or duplications of chromosomes associated with otherwise unexplained euploid miscarriages.
There are several clinical indications for which cytogenetic analysis may be appropriate in early pregnancy loss: (1) the second and subsequent miscarriage(s), (2) miscarriage after assisted reproductive technology, (3) in a known carrier of a structural chromosome rearrangement and (4) in a patient with rheumatic disease, such as systemic lupus erythematosus. An algorithm for evaluation of recurrent early pregnancy loss will be presented, based on performing cytogenetic analysis of the second early miscarriage (Stephenson M, 2006). Identification of chromosome errors in the miscarriage is useful for counselling and for the clinician to decide whether further evaluation is warranted.