12. Cytogenetics of miscarriage Flashcards
What is the definition of a miscarriage?
Spontaneous end of pregnancy at a stage when embryo/fetus is incapable of surviving independently
Up to how many weeks is defined as a miscarriage?
Prior to 24 weeks
After 24 weeks = stillbirth
What are the two common causes of miscarriage at the morula/blastocyst stage?
What happens?
Autosomal monosomy or polyploidy
Fail to implant or lost following transient implantation with little disruption of menstrual cycle
At what stage do the majority of miscarriages in the first trimester take place? Why?
End of first trimester
When placenta takes over nourishment
Of the cases with a chr abnormality that miscarry, what is the cause in the majority?
Single trisomy accounts for 60%
Other than T13, T18, T21, what is the most common trisomy? Is it viable?
T16 in 1% of conceptuses - not viable unless mosaic or CPM
What is the cause of the majority of trisomies? What are the exceptions?
Non-disjunction in maternal meiosis I
T18 - maternal meiosis II
T15 - maternal meiosis I or II
What abnormalities are most commonly seen in second trimester miscarriages?
Viable trisomies (13, 18, 21)
When does Turner syndrome end in miscarriage?
True monosomy X is lethal, conceptions die in utero - Turner patients are mosaic or were in early development
What is the cause of tetraploidy? What are the most common karyotypes?
Failed early mitotic division
92, XXXX and 92, XXYY
What is the cause of the majority of triploidies? What is it called?
2/3 due 2x paternal chromosome sets due to dispermy
Diandry
What is the cause of the minority of triploidies?
2x maternal chromosome sets due to diploid egg
Digyny
What is the consequences of diandric triploidy?
Form partial hydratiform mole
Abort in 1st/2nd trimester, risk of gestational trophoblastic neoplasia
What are the consequences of digynic triploidy?
Non-molar pregnancy, abort early
What is the result of diandric diploidy?
What risk is associated with it?
Complete mole - no embryo
High risk of choriocarcinoma
What is the result of digynic diploidy?
Ovarian teratoma - fatal
What is the definition of recurrent miscarriage?
3 or more miscarriages before 24 weeks
What chromosomal abnormalities cause recurrent miscarriage?
In 2-5% of couples, one partner carries a balanced rearrangement
Most commonly balanced reciprocal translocation or Robertsonian
What 3 types of referral are accepted for testing for miscarriages?
- Pregnancy loss or termination with significant fetal abnormalities
- Pregnancy loss at >24 weeks
- Miscarriage at <24 weeks for 3rd and subsequent
When should parents be karyotyped for RM?
Only if an unbalanced rearrangement is identified in POC
Why should POC be karyotyped before parents?
- To identify unbalanced rearrangment –> allows parents to be tested for balanced translocations
- May also detect causes of sporadic miscarriage (aneuploidy, polyploidy) –> better prognosis for next pregnancy
What tests are generally used for POC?
QF-PCR as first line for aneuploidies (13, 15, 18, 21, 22, X, Y)
Microarray
When does maternal blood need to be tested when testing tissue by QF-PCR?
Normal female result from ESPL or placenta sample
Could represent maternal genotype so mum tested to confirm sample represents the fetus
How does gestation impact the testing available for POC?
<24 weeks IUD - no testing unless recurrent
24-27 weeks IUD - QF-PCR only
> 27 weeks IUD - array (no QF-PCR) as usually cord sample so represents fetal genotype
How are recurrent miscarriage referrals tested?
Must be >3 consecutive miscarriages
QF-PCR prior to array if ESPL or placenta - may require maternal blood
Array if cord/organ/skin
How are POC referrals with fetal abnormality tested?
QF-PCR prior to array if ESPL or placenta - may require maternal blood
Array if cord/organ/skin
Unless isolated neural tube defect –> QF-PCR only
How are positive QF-PCR results followed up?
Karyotype POC to determine nature of aneuploidy and whether there’s a recurrence risk
i.e. due to a familial translocation (high recurrence risk) or non-disjunction (sporadic)
Request parental bloods to determine if they carry a balanced translocation
