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Isaac Blickstein, MD
Generation
of MZ twins
Leonardo da Vinci’s Leda and the Swan
Leda Tyndareus
King of Sparta
Zeus Ruler of gods
Castor Clytemnestra Helene Pollux
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
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
Blickstein I. Twin Res 2000
MZ = embryonic accident
Axioms related to MZ twinning
1. Same prevalence in different populations
2. Corner’s theory of MZ placentation
Example 1:
Fusion not Fission
Fusion not Fission
Example 2:
DZ MC twins
3a. High malformation rate
•PTD/vPTD
•VLBW/ELBW
•Brain damage
3b. Very high perinatal risk
4. All methods of ART increase MZ splitting
Mechanism – Unknown
Familial
Recurrent MZs:
1/250 X 1/250 = 1/62,500
The potential role of the
ELABELA peptide
hormone in the
generation of MZ twins
Bruno Reversade
Experimental halving of the embryo (different mares)
Involution of a co-dominant axis
Evolution of a co-dominant axis
Evolution of a co-dominant axis
Blastomere herniation theory
Cell repulsion theory
Trigger Zygotic
splitting
Anomalies
•Fetal
•Placental
Infertility treatment Zygotic
splitting Anomalies
Infertility treatment = teratogen*
*Fulfilling 5/6 Wilson’s Six Principles of Teratology
Unanswered
questions
Day 3 IVF embryo. Where is the split ?
Why some zygotes split and
others do not split ?
Image: M. Ropacka
How do we explain MC triplets ?
De Lia, June 5, 2008
How do we explain MZ triplets ?
How do we explain MZ quadruplets ?
How do we explain MZ quintuplets ?
h. Sapiens Nine-banded Armadillo
Polyembryony occurs in two mammalian species
The theory
1. The ovary (irrespective of
race) contains oocytes with an
inborn propensity to undergo
splitting after fertilization
1/250
Spontaneous
Ovulation induction
Selection of splitting-prone oocyte is at random
OI increases the chance of selection
0
4
8
12
16
Spontaneous ART hMG Clomiphene
RR
EFPTS, 2004
Blickstein et al, 2003
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
Observations in the Armadillo:
• Always produce MZ offspring
• Uterus simplex
Observations in the Armadillo: • Delayed implantation (3-4 months)
• Implantation in predestined uterine locus
• 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.
2. The inborn propensity is to
undergo to undergo binary
splitting
Derom, 1986
This explains MZ quadruplets
This explains MZ triplets
This suggests 3 types of MZ twins
This explains MZ twins
Singleton, but with
characteristics of an MZ twin
Bocklage, 1980
Singleton, but with
characteristics of an MZ twin
Bocklage, 1980
3. The zona pellucida controls
the timely hatching
Where is the split ?
4. There is no ‘physical’ split
as long as the zona pellucida is
intact
This explains why splits are not seen in
‘regular’ IVF
De Lia’s asymmetry configurations
Summary:
Fertilization of a splitting-
prone oocyte may lead to
ZP-controlled binary
splitting
Thank
you !
