The prevalence of abnormal parental karyotypes in couples with a history of recurrent pregnancy losses are estimated to be 1.9 – 3.8%.

Introduction

Some couples who have suffered recurrent pregnancy loss may request parental karyotyping to identify a chromosomal abnormality. The presence of a balanced translocation leads to abnormal chromosomal arrangements in the gametes, and therefore aneuploidy in the embryo.

The prevalence of abnormal parental karyotypes in couples with a history of recurrent pregnancy losses are estimated to be 1.9 – 3.8%.1 This is a 5-10 fold increase compared to the general population. However, it should be noted that couples affected with a balanced translocation also have an 83% chance of having a healthy child from natural conception.1

The risk of recurrent pregnancy loss depends on the nature of the genetic abnormalities found. There is a higher risk of miscarriage in those with balanced translocations and inversions compared to those with Robertsonian translocations or other types of genetic differences.2 Some translocations also confer an increased risk of seriously affected stillborn or live born infants, so detailed genetic guidance should always be obtained.

Pre-implantation genetic testing for structural rearrangements (PGT-SR) offers a solution for couples with balanced translocations wishing to avoid any risk of an unbalanced conception.

The probability of abnormal parental karyotypes in unselected population is estimated to be very low. In particular, parental genetic testing is likely to be of limited value for the couples of older ages, fewer than 3 pregnancy losses or in absence of any relevant family history.

Bullet point guidance

  • Genetic analysis of parents should be considered following individual assessment of the clinical history or if indicated by the results of the genetic analysis of pregnancy tissue from previous losses.
  • Where an unbalanced translocation is identified in the pregnancy tissue, parental karyotyping should be organised, with onward referral to clinical genetics in the case of abnormal results.
  • Parental karyotype should be considered for women with ³5 previous miscarriages, or ³2 miscarriages and a history of ³3 miscarriages in their siblings or parents.3
  • Recurrent pregnancy loss clinic staff should be aware of the likely timelines needed for the genetics laboratory to provide the parental karyotyping result. Usually, this interval is approximately four weeks.
  • If a parental genetic abnormality is found, the couple should be referred to a clinical genetics team for further counselling.
  • Where parental balanced translocations are diagnosed, patients should be referred to a regional centre for consideration of PGT-SR.

References

  1. E Franssen MTM, Korevaar JC, Van Der Veen F, Leschot NJ, Bossuyt PMM, Goddijn M. Reproductive outcome after chromosome analysis in couples with two or more miscarriages: Case-control study. British Medical Journal 2006.
  2. ESHRE Early Pregnancy Gudeline Development Group. Recurrent Pregnancy Loss. European Society of Human Reproduction and Embryology (ESHRE). 2017. 1–154.
  3. van den Berg, M.M., et al., Early pregnancy care over time: should we promote an early pregnancy assessment unit? Reproductive Biomedicine Online, 2015. 31(2): p. 192-8.