Recurrent miscarriage: genetic factors and assessment of the embryo.

In recurrent pregnancy loss, current practice often fails to make a diagnosis, as the fetal causes of pregnancy loss are usually ignored and only the maternal factors are assessed. Hence, it has been almost impossible to show that any treatment has an effect. This presentation is concerned with the fetal causes of recurrent pregnancy loss. The maternal causes are well known and include: uterine factors, antiphospholipid syndrome, possibly hereditary thrombophilias, alloimmune factors, infections, and endocrine abnormalities. However, all assessments of these factors have been confounded by the presence of abnormal embryos that may themselves be incompatible with life. The fetal causes of embryo loss include structural malformations that are incompatible with life, and chromosomal aberrations. Structural malformations Structural aberrations have been found in laboratory animals and may explain some pregnancy resorbtions [1]. Resorbtion of pregnancies in laboratory animals can be considered to be the equivalent of missed abortions in humans. In human pregnancy ultrasound is the main means of diagnosing fetal structural abnormalities. However, 89% of human recurrent miscarriages occur in the first trimester [2]. At that stage the embryo is too small to be diagnosed as normal or abnormal on ultrasound. Indeed, 70% are reported to be blighted ova [2]. Philipp et al. [3] performed embryoscopy on missed abortions just prior to curettage and found developmental defects in 200/233 missed abortions (85%). These defects included anencephaly, encephalocele, spina bifida, syndactyly, pseudosyn-dactyly, polydactyly, cleft hand and cleft lip. They karyotyped 221 embryos, of which 56 (25%) were eukaryotypic. However, 20 of the eukaryotypic embryos (35.7%) were grossly disorganized. Without embryoscopy these embryos would not have been diagnosed, and the patient might have been treated empirically with hormone supplements, anticoagulants, etc., all for a presumed maternal factor. In a later series Phillip [4] showed how sonograms of first-trimester missed abortions may appear normal, but can be seen to be grossly abnormal on embryoscopy. Once the second trimester is reached, ultrasound can pick up structural malformations. These malformations are usually associated with a normal karyotype. However, expert ultrasound is required for diagnosis. Chromosomal aberrations Regarding chromosomal aberrations, our team has carried out a number of studies to determine both the incidence of chromosomal aberrations in recurrent pregnancy loss and the chance of a subsequent live birth after aborting a chromosomally normal or abnormal embryo. As patients often present in the interval between miscarriages, and karyotyping of the abortus has not always been …