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Key Points

  • Disease summary:

    • Recurrent pregnancy loss (RPL) is traditionally defined as three or more consecutive losses of recognized pregnancies in the first or early second trimester (<20 weeks of gestation). Sporadic spontaneous pregnancy loss occurs randomly in one-sixth of clinically recognized pregnancies. However, RPL must be distinguished from sporadic cases as these occasionally respond to treatment. Around 1% of couples attempting pregnancy experience RPL.

  • Hereditary basis:

    • Structural chromosomal abnormalities such as translocations and inversions are often identified in one partner of a couple experiencing RPL. The fetuses from these couples frequently carry chromosome copy number abnormalities which lead to miscarriage. Hereditary thrombophilia in females is also occasionally associated with RPL.

  • Differential diagnosis:

    • RPL is a heterogeneous condition. In addition to parental chromosomal abnormalities and hereditary thrombophilia, hormonal and metabolic disorders, uterine anatomic abnormalities, certain infections, and autoimmune disorders have been accepted as etiologic factors in RPL. However, up to 50% of these cases still remain unexplained after standard gynecologic, hormonal, and karyotypic investigations.

Diagnostic Criteria and Clinical Characteristics

Diagnostic Criteria

RPL is traditionally defined as three or more consecutive losses of a recognized pregnancy in the first or early second trimester (<20 weeks of gestation).

Clinical Characteristics

Chromosome Abnormalities

In 2% to 4% of couples experiencing RPL, a balanced structural abnormality is found in one partner. Chromosomal translocations are the most common structural abnormalities associated with early RPL. Robertsonian translocations involve the centric fusion of two acrocentric chromosomes (numbers 13, 14, 15, 21, and 22). Balanced carriers of Robertsonian translocations have no clinical symptoms, but often produce chromosomally unbalanced gametes. These numerical abnormalities in the autosome usually result in early fetal death, or occasionally in the birth of children with trisomy 13 or 21 (Fig. 99-1).

Figure 99-1

Chromosome Segregation in Balanced Translocation Carriers. Segregation of translocation and relevant chromosomes in balanced carriers for a t(14;21) Robertsonian translocation. Conceptuses are most often aneuploidy, resulting in miscarriage. Occasionally carriers give birth to a child with a normal or balanced karyotype, although some newborns are affected by trisomy 21.

Other reciprocal translocations also cause RPL. During gametogenesis, paternal and maternal chromosomes undergo homologous pairing and recombine to segregate correctly in meiosis I. In balanced carriers of reciprocal translocations, normal and translocated chromosomes form an abnormal meiotic configuration that often leads to partially unbalanced gametes (Fig. 99-2). Large chromosomal imbalances result in fetal death, while chromosomally unbalanced children might be born if regions involved are small.

Figure 99-2

Meiotic Configuration During Gametogenesis in Balanced Translocation Carriers. Meiotic configuration during gametogenesis in balanced carriers of a t(11;22) reciprocal translocation. In adjacent 1 or 2, conceptuses harbor a partial trisomy and partial monosomy resulting in early pregnancy loss. Occasionally carriers give birth with a normal or balanced karyotype, while <1/10 newborns are affected by +der(22) syndrome (Emanuel syndrome) through a 3:1 segregation.

Other structural abnormalities such as inversions or insertions can also cause RPL.

Hormonal ...

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