cytogenetics of miscarriage

Question 1

Chromosome abnormalities in POCs from spontaneous miscarriage:

Answer 1

Autosomal trisomy 60%
45,X 20%
triploidy 15%
Other (eg structural, tetraploidy) 5%

Question 2

What % of oocytes and sprem are chromosomally abnormal

Answer 2

Oocyte (20-25% )

Sperm (~10%)

Question 3

What is the most prevalent of the trisomies?

Answer 3

Trisomy 16 but not compatible with life in non-mosaic form. Miscarriage usually occurs in first trimester.

Question 4

How many foetuses abnormal in first trimester?

Answer 4

10%. 10-15% end in spontaneous abortion towards end of trimester when placenta takes over nourishment for fetus and the body recognises the abnormal development.

Question 5

How many foetuses abnormal in second trimester?

Answer 5

20%. Chromosome abnormalities may be present in ~50% losses but more likely to be the ‘viable’ trisomies: +21 (63%), +18(23%), +13(13%), other (1%).

Question 6

How many foetuses abnormal in third trimester?

Answer 6

Only a small fraction due to chromosome abnormality (~5%). Most common = +18.

Question 7

Chromosome abnormality loss rates:

Answer 7

Trisomy 21	              80%
Trisomy 13, 18	               95%
45,X	                       >95-99%
Balanced structural	15%
Normal                             8%

Question 8

how many 45,X due in utero?

Answer 8

almost all 99%.hypothesised that all Turner syndrome patients may be mosaic, or once were in early development.

Question 9

80% of cases the single X chromosome in 45, X is of which origin?

Answer 9

maternal

Question 10

How many women experience recurrent miscarriage?

Answer 10

~1%

Question 11

The Royal College of Obstetricians and Gynaecologists (RCOG) define recurrent miscarriage as:

Answer 11

three or more miscarriages before 24 weeks post-menstruation

Question 12

Causes of miscarriage:

Answer 12

• epidemiological
• genetic abnormalities
• anatomic/structural abnormalities (e.g. of the uterus, cervical weakness etc)
• maternal endocrine and immune response anomalies (eg: Antiphospholipid syndrome, thyroid dysfunction)
• infective agents
• acquired thrombophilic defects
• unexplained

Question 13

balanced structural chromosome rearrangements thought to be present in what % recurrent miscarriage couples?

Answer 13

2-5%