研究グループ

For patients with recurrent pregnancy loss

Environment and Children’s Study (JECS)

The four major causes of miscarriage are antiphospholipid syndrome (APS), a congenital uterine anomaly, chromosomal structural rearrangement in either partner, and fetal (embryonic) chromosomal aneuploidy (1, 4-6). Antiphospholipid antibodies are found in 10% of cases, chromosomal rearrangement abnormalities in 6%, and uterine malformations in 3.2% (Fig. 2-A). The prevalence of APS that meets the definition of the International Society for Antiphospholipid Antibodies is about 4% (6). Endocrine abnormalities include diabetes hypothyroidism, as well as polycystic ovary syndrome, but the latter is still controversial.

Figure 2:Distribution of causes of recurrent pregnancy loss

Distribution of causes of recurrent pregnancy loss

1676 couples
Sugiura-Ogasawara et al. Fertil Steril 2010

 

Distribution of causes of recurrent pregnancy loss

482 couples
Sugiura-Ogasawara et al. Hum Reprod 2012

The four major causes of RPL at this time are listed below (Table 3).

  1. Antiphospholipid syndrome
  2. Congenital uterine anomaly
  3. Chromosomal structural rearrangement in either husband or wife
  4. Fetal or embryonic chromosome aneuploidy

Because fetal chromosome testing is not covered by health insurance in Japan and can only be performed in a limited number of facilities, it is rarely performed on fetuses of past miscarriages in patients who come in for their first visit. Therefore, RPL of "unknown cause" comprised 69 % of the cases (Fig. 2-A). However, when properly examined, 41% of fetuses showed chromosome aneuploidy, a rate which increased with the age of the woman (Fig. 2-B, ref. 5). The frequency of cases with a truly unknown cause was about 25%. Recommended tests are listed in Table 3 and the details are explained item by item.

Table 3: Examination and management of patients with recurrent pregnancy loss

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Causes Examination management
Antiphospholipid Syndrome
  • Lupus anticoagulant
    Two kinds of tests should be performed
  • (b2GPI dependent) anticardiolipin antibody
  • Since results of both tests are often false positives, a diagnosis of antiphospholipid syndrome is made when the positive status persists for intervals of 12 weeks or more.
  • Low dose aspirin and heparin intake during pregnancy
  • 70-80% of patients have live births
Congenital uterine anomaly Ultrasound sonography
  • It is not yet established whether surgery improves the live birth rate.
Chromosomal rearrangement abnormalities (Translocation) Chromosome karyotype
  • It is not yet established whether PGT-SR improves the live birth rate.
Fetal or embryonic chromosome aneuploidy Chromosome karyotype in products of aborted conception
  • It is not yet established whether PGT-A improves the live birth rate.

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