The timing of fetal demise provides etiologic clues and its documentation is important in investigations into causes and treatments for recurrent pregnancy loss. The vast majority of preclinical and early clinical pregnancy losses are the result of de novo fetal aneuploidy (10). This is also thought to be the cause of anembryonic pregnancy losses, whereas pregnancy losses occurring after 10 weeks of fetal development are much less likely to derive from fetal aneuploidy. Pregnancy losses resulting from de novo fetal aneuploidy, whether early and undocumented or documented through evaluation of chromosomal content in fetal tissues, cloud the results of many published studies. Their presence or absence must be documented in all investigations on recurrent pregnancy loss patients and their potential as a confounding factor discussed. The timing of fetal demise and tissue chromosomal analysis of any collected fetal tissues should be carefully weighed when diagnostic and therapeutic investigations into causes of recurrent pregnancy loss are being considered.
Genetic Factors The most common inborn parental chromosomal abnormalities contributing to recurrent abortion are balanced translocations (11–14), in which one parent carries an overall normal gene content, but has a piece of one chromosome inappropriately attached to another.
Table 33.1 Proposed Etiologies for Recurrent Spontaneous Abortion
Table 33.1 (Continued )
TH, T helper; MTHFR, methylene tetrahydrofolate reductase; APS, antiphospholipid antibody syndrome.
Depending on the nature of the translocation (reciprocal or Robertsonian), the gametes produced by the translocation carrier will be normal (reciprocal only), balanced, or unbalanced for the translocated DNA. When fertilized by a chromosomally normal gamete, the resulting embryos may be chromosomally normal (reciprocal only) or may be balanced or unbalanced carriers of the translocation. Most gametes and embryos with abnormal chromosomal status will not survive. Of those that do, live offspring will either be carriers of a balanced translocation or, for Robertsonian translocations, be monosomic or trisomic for the translocated chromosomal DNA.
Among the possible chromosomal monosomies, only that of the X chromosome typically permits viable offspring. On careful examination, however, many of these offspring may, in fact, exhibit mosaicism. Embryonic chromosomal monosomy may be particularly prevalent among patients with histories of recurrent pregnancy loss who are undergoing in vitro fertilization (IVF) (15). Compared with monosomies, chromosomal trisomies (e.g., trisomy 13, 18, and 21) appear to be tolerated a bit more readily, although mosaicism also may be implicated with these abnormalities.