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(1)

Isaac Blickstein, MD

Generation

of MZ twins

(2)

Leonardo da Vinci’s Leda and the Swan

Leda

Tyndareus King of Sparta

Zeus Ruler of gods

Castor Clytemnestra Helene Pollux

(3)

JM Thijssen. Twins as monsters: Albertus

Magnus theory of the generation of twins and

its philosophical context.

Bull Med Hist 1987; 61:237-46

Albertus Magnus (ca 1200-80), Albert the Great, doctor universalis

(4)

Albertus Magnus:

Therefore it is dangerous that the female moves

during sexual intercourse in the way prostitutes are reputed to do, because if at such moment they

would conceive, they

could generate an awful two-headed monster”

Twins are a divine

punishment for misbehaving

(5)

Blickstein I. Twin Res 2000

(6)

MZ = embryonic accident

(7)
(8)

Axioms related to MZ twinning

(9)

1. Same prevalence in different populations

(10)

2. Corner’s theory of MZ placentation

(11)
(12)
(13)

Example 1:

Fusion not Fission

(14)

Fusion not Fission

(15)

Fusion not Fission

(16)
(17)
(18)

Example 2:

DZ MC twins

(19)
(20)
(21)

3a. High malformation rate

(22)

•PTD/vPTD

•VLBW/ELBW

•Brain damage

3b. Very high perinatal risk

(23)

4. All methods of ART increase MZ splitting

(24)
(25)

Mechanism – Unknown

(26)

Familial

Recurrent MZs:

1/250 X 1/250 = 1/62,500

(27)
(28)
(29)
(30)

The potential role of the ELABELA peptide

hormone in the

generation of MZ twins

Bruno Reversade

(31)

Experimental halving of the embryo (different mares)

(32)

Involution of a co-dominant axis

(33)
(34)

Evolution of a co-dominant axis

(35)

Evolution of a co-dominant axis

(36)
(37)

Blastomere herniation theory

(38)

Cell repulsion theory

(39)
(40)
(41)

Trigger Zygotic splitting Anomalies

•Fetal

•Placental

(42)

Infertility treatment Zygotic splitting Anomalies

Infertility treatment = teratogen*

*

Fulfilling 5/6 Wilson’s Six Principles of Teratology

(43)

Unanswered

questions

(44)

Day 3 IVF embryo. Where is the split ?

(45)

Why some zygotes split and others do not split ?

Image: M. Ropacka

(46)

How do we explain MC triplets ?

De Lia, June 5, 2008

(47)

How do we explain MZ triplets ?

(48)

How do we explain MZ quadruplets ?

(49)

How do we explain MZ quintuplets ?

(50)

h. Sapiens Nine-banded Armadillo

Polyembryony occurs in two

mammalian species

(51)
(52)
(53)

The theory

(54)
(55)
(56)

1. The ovary (irrespective of

race) contains oocytes with an

inborn propensity to undergo

splitting after fertilization

(57)

1/250

Spontaneous

Ovulation induction Selection of splitting-prone oocyte is at random

OI increases the chance of selection

(58)

0 4 8 12 16

Spontaneous ART hMG Clomiphene

RR

EFPTS, 2004 Blickstein et al, 2003

(59)

1. The ovary (irrespective of race) contains oocytes with an inborn propensity to undergo splitting after fertilization

Explains why

• Similar prevalence of spontaneous MZs in different races

• Prevalence increases after all methods of infertility treatment

(60)

Observations in the Armadillo:

• Always produce MZ offspring

• Uterus simplex

(61)

Observations in the Armadillo:

• Delayed implantation (3-4 months)

• Implantation in predestined uterine locus

(62)

The armadillo’s uterus forms a space that

allows no more than one blastocyst to implant

• In order to produce

more offspring (= reproductive fitness) the blastocyst undergoes two binary divisions.

(63)

2. The inborn propensity is to undergo to undergo binary

splitting

(64)

Derom, 1986

(65)

This explains MZ quadruplets

(66)

This explains MZ triplets

(67)

This suggests 3 types of MZ twins

(68)
(69)
(70)
(71)
(72)
(73)

This explains MZ twins

(74)
(75)

Singleton, but with

characteristics of an MZ twin

Bocklage, 1980

(76)

Singleton, but with

characteristics of an MZ twin

Bocklage, 1980

(77)

3. The zona pellucida controls

the timely hatching

(78)
(79)

Where is the split ?

(80)

4. There is no ‘physical’ split

as long as the zona pellucida is

intact

(81)
(82)

This explains why splits are not seen in

‘regular’ IVF

(83)
(84)
(85)
(86)

De Lia’s asymmetry configurations

(87)
(88)
(89)
(90)

Summary:

Fertilization of a splitting- prone oocyte may lead to ZP-controlled binary

splitting

(91)

Thank

you !

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