14. Multiple pregnancies

Question 1

Explain what are the types of twins?

Answer 1

Twins can be:
- dizygotic (DZ) - fraternal - % increased with IVF - separate eggs+separate sperm - separate zygotes
- monozygotic (MZ) - identical - same egg+sperm split into two zygotes
- sesquizygous - semi-identical - double fertilisation - two ICMs

Question 2

What is a multiple pregnancy?

Answer 2

Multiple pregnancy - when woman falls pregnant with 2+ fetuses at the same time

Question 3

Explain wha are the types of triplets?

Answer 3

Triplets can be:
- monozygotic (splits x3) - 3 identical
- dizygotic + monozygotic (one dizygotic splits x2) - 2 identical + 1 fraternal
- trizygotic (three separate eggs + separate sperm) - fraternal triplets

Question 4

Explain different chorionicities in twins

Answer 4

Chorionicity - what structures the twins share - placenta (chorion)/ amnion - depends when zygote split

Twin chorionicities:
- if monozygotic late split - share both placenta and amnion - monochorionic (MC) + monoamniotic (MA) -> MC/MA
- if monozygotic earlier split - share placenta but not amnion - monochorionic (MC) + diamniotic (DA) -> MC/DA
- if dizygotic twins - completely separate - dichorionic (DC) + diamniotic (DA) -> DC/DA

=> monozygotic twins can also be DC/DA if split very early

Question 5

Can monozygotic twins have separate placentas?

Answer 5

Yes - if split very early - can have separate placentas + separate amnions like dizygotic twins - still identical

Question 6

When can monozygotic twins split?

Answer 6

The time when MZ twins split - determine what level of sharing they have - if split:
- early - days 1-3: DC/DA - separate placentas + amnions
- mid - days 4-8: MC/DA - same placenta + separate amnions
- late - days 8-13: MC/MA - same placenta + amnion

=> sharing depends on development - placenta develops first - shared earlier than amnions

Question 7

What event determines if the split embryo has one or two placentas (chorions)?

Answer 7

Placenta (chorion) sharing depends if the zygote split before / after formation of TE at day 5

Trophoblast - chorions - placenta

Question 8

What event determines if the split embryo has one or two amnions?

Answer 8

Amnion sharing depends if the zygote split before / after amnion formation

Question 9

How do conjoined twins form?

Answer 9

If the split occurs at days 13-15 and ICM doesn’t completely separate / secondarily rejoins => conjoined twins

Born physically connected - may share one or more internal organs - can be surgically separated - many are stillborn

Question 10

Explain what is twin-twin transfusion syndome (TTTS)

Answer 10

Twin-twin transfusion syndome (TTTS) - occurs in MC/DA pregnancies - share placenta but one fetus forms higher vascular network than the other - receives most of the blood flow - more nutrients while the other twin is compromised - born smaller due to malnourishment

Question 11

Explain what are mirror image twins

Answer 11

Mirror image twins - **healthy MZ **twins which show inverse laterality - twinning occurred after embryonic cells began to lateralise but before primitive streak formation - ex: same moles / wrinkles / toothing / handedness but on opposite sides

Question 12

What are the factors influencing multiple pregancy births?

Answer 12

Multiple pregnancies determined by:
- IVF - multiple embryo transfer
- age - multiple follicle ovulation
- genetic predisposition - certain mutations induce multiple follicle ovulation

Question 13

Explain what is the ‘one at a time’ policy and why was it implemented?

Answer 13

‘One at a time’ policy encourages single embryo transfer:
in IVF ovaries overstimulated - many embryos generated - to increase success % - multiple ET + chance of splitting -> higher** maternal risk** + preterm birth

Question 14

Does ART lead to MZ twinning?

Answer 14

MZ twinning - embryo splitting after ART has been observed x2-5 more - potentially suspected but not proved:
- media used in IVF affects ZP - hardens - problems in embryo hatching -> split
- IVF/ICSI procedures create holes in ZP -> induces a split

Question 15

How does maternal age affect multiple pregnancies?

Answer 15

Chance of multiple pregnancy increases with maternal age - because higher chance of multiple ovulations:
HPO axis: lower PMF reserve - less granulosa cells secreting inhibin -> less supressed FSH -> more FSH secreted by pituitary - support maturation of several follicles

Question 16

Why would double ovulation be evolutionary favourable?

Answer 16

With increased maternal age - higher chance of fetal mortality -> create a PMF system for supporting double ovulation when reserve decreases

A strategy to maximise reproductive success at later age

Question 17

What are the potential targets of genetic predisposition for DZ twinning?

Answer 17

DZ twins more likely to have dizygotic twins - more common in some ethnic groups - DZ twinning run on maternal side (because of double ovulation) + some specific genes involved in folliculogenesis pathway:
- BMP15 mutation - increases twinning
- GDF9 mutation - increases twinning
- sequence variation in FSH, SMAD3 loci - increases chance of twinning

Question 18

Is it known what causes MZ twinning?

Answer 18

Not known what causes zygotes to split -> monozygotic twins - all pregnant women have same chance of splitting - but rarely familial MZ twinning seen - may be inherited defect due to chance - possibly in one of ZP proteins / mutation of cell-to-cell recognition and adhesion

Question 19

Explain what are semi-dentical twins

Answer 19

**Semi-identical **- sesquizygous - twins - single oocyte double fertilisation + splitting - 50% identical (on maternal side) and 50% different (on paternal side)

Question 20

Explain how is semi-identical twinning possible

Answer 20

Double / dispermic fertilisation of single oocyte - 3 PN (1 maternal + 2 paternal) align in tripolar spindle apparatus - 3 genetically distinct cells at cleavage - one of them only paternal genome - won’t develop - other two maternal + paternal homologs - each type dominates an ICM - but both ICM chimeric (genetically mosaic) - form MC/DM twins - share 75% of DNA

Question 21

Are MZ twins actually genetically identical?

Answer 21

eNo - MZ twins have same genomes but epigenetics + accummulated mutations

Question 22

What could be an SNP analysis of sesquizygous vs fraternal vs identical twins?

Answer 22

Question 23

Are MZ twins actually identical?

Answer 23

In beginning genetics yes - but then mutations accummulate + epigenetics - different interpretations of the same genome