L15: Multiple Pregnancy Flashcards

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1
Q

What are the different types of twins?

A
  • Dizygotic (DZ)
  • monozygotic (MZ)
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2
Q

What are the differences between monozygotic and dizygotic twins?

A

monozygotic:
- 1/3 of twins
- one egg and one sperm
- zygotes are genetically nearly identical
- share all DNA
- twins appear identical
- always same sex

dizygotic:
- 2/3 of twins
- two eggs and two sperm
- zygotes have different genetic constitutions
- share 50% of DNA
- twins have no more resemblence than any brothers or sisters
- can be of different sex

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3
Q

What is the frequency of monozygotic and dizygotic twins?

A
  • monozygotic - 1/3 twins
  • dizygotic - 2/3 twins
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4
Q

How much are genetically monozygotic and dizygotic twins similar?

A

monozygotic - genetically nearly identical, share all DNA
dizygotic - different genetic constitutions, share 50% of DNA

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5
Q

What are the possible sexes of monozygotic and dizygotic twins?

A
  • monozygotic always same sex
  • dizygotic can be same or different sex
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6
Q

How can triplets be derived?

A
  • one zygote and all be identical
  • two zygotes, consisting of identical twins and a singleton
  • three zygotes and be of the same sex or of different sexes
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7
Q

How do twins develop in the uterus? (chorionicity)

A
  • monochorionic monoamniotic (share chorion and amnion; MC/MA; share placenta)
  • Monochorionic diamniotic (share chorion, but two amnions; MC/DA, share placenta)
  • Dichorionic diamniotic (two chorions, two amnions; DC/DA; everything separate)

check L15, slide 6

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8
Q

What is the most frequent chorionicity of monozygotic and dizygotic twins?

A
  • for monozygotic most frequent is monochorionic diamniotic
  • for dizygotic it’s always dichorionic diamniotic
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9
Q

How is chorionicity determined?

A

The degree of splitting is determined by the timing of the split:
- at days 1-3 - DC/DA
- at days 4-8 - MC/DA
- at days 8-13 - MC/MA

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10
Q

When does chorion and amnion post-fertilisation begin to form?

A
  • chorion forms 4-5 days post-fertilisation
  • amnion begins to form on day 8
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11
Q

How are two complete and separate chorions/amnions determined?

A

Twins who have two complete and separate chorions indicates that separation occured before the formation of the trophoblast tissue on day 5

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12
Q

How are separate amnions but same chorion determined?

A

In pregnancies where twins share a chorion, suggests that split occurred within the ICM after the trophoblast formed. If they have separate amnions: suggests the split occured before the formation of the amnion (day 9)

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13
Q

How are shared amnion and chorion determined?

A

If separation of ICM comes after formation of chorion and after the formation of amnion then resulting embryos would have one chorion and one amnion

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14
Q

What are conjoined twins?

A

The two fetuses will remain physically connected (most often at the chest, abdomen or pelvis), conjoined twins may also share one or more internal organs

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15
Q

How does conjoined twinning occur?

A

if separation of an embryo occurs between day 13 & 15 & the inner cell mas does not completely separate, or if portions of the inner cell mass secondarily re-join, conjoined twins may result

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16
Q

What’s the survival rate of conjoined twins?

A

Many are stillborn or die shortly after birth; some can be surgically separated

17
Q

What is twin-twin transfusion syndrome?

A
  • TTTS occurs in around 10-15% of MC/DA pregnancies;
  • placental vascular anastomoses form so that one twin receives most of the blood flow.
  • Flow to the other twin is compromised.
  • One twin is usually larger than the other
18
Q

What are mirror image twins?

A
  • Mirror-image monozygotic twins have inverse laterality;
  • suggests that twinning event took place after the cells of the embryonic plate were beginning to lateralise but before formation of the primitive streak.
19
Q

What are the examples of mirror image twins?

A
  • whether the first tooth erupts on the right or let side
  • which side cowlicks or hair whorls are present
  • handedness
  • wrinkles
  • position of warts
  • type and presence of neuralgias
20
Q

Why is the incidence of twins/triplets more common nowadays?

A
  • The incidence of twins, triplets or more is common due to assisted reproductive technologies (ART) and fertility treatments;
  • transfer of more than one embryo can lead to dizygotic twins.
  • campaigns such as ‘one at a time’ have helped raise awareness about multiple births and helped protect health of women and their babies
21
Q

Does having ART increase your chances of having monozygotic twinning? What are the resons for it?

A
  • 2x-5x amount of MZ twins born following IVF
  • The reason is thought to be zona pellucida
  • Maybe there is something in the media of IVF used that causes zona hardening. So that when the blastocyst is about to implant and it hatches, that there are problems with hatching that lead to twinning of embryo
  • It is also speculated that handling the embryo during IVF creates breaks/holes in the zona pellucida that might alter the embryo and increase its chances of twinning
22
Q

What is the cause of higher incidence of having dizygotic twins?

A

Women aged 35+ twice as likely to have DZ twins than women under 25; percentage of cycles that show spontaneous multiple follicle growth:
- older women –> 25%
- younger women –> 5%

23
Q

What is the reason for older women having dizygotic twins more often?

A
  • DZ twinning associated with DZ twinning
  • It is related to HPO axis, as the woman is young there is lots of follicles, thus lots of inhibin produced, which causes negative feedback on pituitary
  • As the woman gets older, there will be fewer follicles, fewer granulosa cells, less inhibin, therefore less negative feedback and therefore more FSH produced, more follicles stimulated, increases rate of follicle growth and chance of double ovulation
24
Q

Is there a genetic predisposition to dizygotic twins?

A

Dizygotic twins:
- there are some factors that make having fraternal twins more likely: they are more common in some ethnic groups; DZ twins can run on the mother’s side of the family
- follicular growth, maturation and ovulation are tightly regulated via various pathways
- ovarian folliculogenesis and determination of ovulation quota are controlled both by circulating concentrations of FSH and by intra-ovarian factors including the two oocyte growth factors, GDF9 and BMP15, as well as their cognate receptors
- mutations in BMP15 and GDF9 have been associated with increased DZ twinning in sheep and humans
- sequence variation at the FSH and SMAD3 loci increases the odds of DZ twinning in women

25
Q

Is there a genetic predisposition to monozygotic twins?

A

monozygotic twins:
- not known what causes MZ twins
- tend to not run in families
- all pregnant women have same chance of having MZ twins
- but very rarely, familial monozygotic twinning is seen

26
Q

What are the possible reasons for a very rare familial monozygotic twinning?

A
  • BUT, very rarely, familial monozygotic twinning is seen
    i) Can be transmitted by both the father and the mother
    ii) Suggests that in familial monozygotic twinning, there may be an inherited effect
    iii) Possibly a defect in one of the zona pellucida proteins
    iv) A fragile zona pellucida might allow early separation of clumps of blastocyte
    v) Mutation in a gene that leads to failure/delay of cell-to-cell recognition and adhesion
27
Q

What are sesquizygotic twins?

A
  • Semi-identical twins, after SNP analysis compared genotypes between twins,
  • revealed that twins share and identical maternal allele, but chimeric for two separately identical paternal alleles;
  • both twins had the same maternal copy but different paternal alleles;
  • only two cases in the world; maybe one egg fertilized by two sperms
28
Q

What is the possible mechanism for sesquizygotic twinning?

A
  • Case of dispermic fertilization – shouldn’t be normally possible (one carrying X, one carrying Y)
  • Results in three pronuclei: maternal and two paternal nuclei
  • Then heterogoneic cleavage division takes place, which is a tripolar spindle apparatus instead of bipolar
  • Three cells will form, two will be biparental lineage and one will be only paternal lineage
  • Biparental cell lines would outcompete uniparental lines, where twinning then occurs
  • They are chimeras: one twin was made up proportionally from one type of cells, while the other was made from other types of cells
29
Q

Are monozygotic twins really identical?

A

Recent study sequenced whole genome twin pairs, their parents, partners and offspring;
- identified post-zygotic mutations and timed their occurrence by relating them to the specification of primordial germ cells (PGCs)
- identified mutations present in offspring but absent in partner/twin sibling
- estimated that on avergae 5.2 pre-PGCs mutations exist between twin genomes (but very variable)
- 15% of probands had pre-PGCs mutations that were then passed onto their offspring (but absent in their twin sibiling)
- found that no two genomes are identical, not even the genomes of ‘identical’ twins